Locus Summary

Gene:MIRLET7B; microRNA let-7b
Aliases: LET7B, let-7b, MIRNLET7B, hsa-let-7b
Summary:microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Databases:miRBase, OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 29 August, 2019

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 29 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 29 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (9)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

MicroRNA Function

Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.

TissueTarget Gene(s)Regulator(s)MIRLET7B Function in CancerEffect
skin (2)
-melanoma (2)
CCND1 (1)
inhibit cell proliferation (1)
induce apoptosis (1)
inhibit cell cycle progression (1)
inhibit anchorage-independent cell growth (1)
tumor-suppressive (2)
liver (1)
-hepatocellular carcinoma (1)
inhibit cell proliferation (1)
induce apoptosis (1)
tumor-suppressive (1)
blood (1)
-diffuse large B-cell lymphoma (1)
PRDM1 (1)

Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.

Latest Publications: MIRLET7B (cancer-related)

Zhang W, Zhao W, Ge C, et al.
Decreased let-7b is associated with poor prognosis in glioma.
Medicine (Baltimore). 2019; 98(22):e15784 [PubMed] Related Publications
Abnormal expression of let-7b has been observed in many tumors, including glioma. However, the clinical significance of let-7b in glioma remained unclear. The aim of the study was to explore the correlation of let-7b expression with clinicopathological factors and prognosis in human glioma.Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the relative expression of let-7b in glioma tissues. The association of let-7b expression with clinicopatholoigcal features of glioma patients was estimated using chi-square test. Overall survival curves were plotted using Kaplan-Meier method with log rank test. The prognosis analysis was performed using Cox regression model, and the results were shown as hazard ration (HR) with 95% confidence interval (CI).The relative expression of let-7b was significantly lower in glioma tissues than that in normal brain tissues (P < .001). Furthermore, let-7b level was closely correlated with World Health Organization (WHO) grade (P = .027) and Karnofsky performance score (KPS) (P = .018). Survival analysis indicated that glioma patients with low let-7b expression had significantly shorter overall survival time than those with high expression (log rank test, P < .001). Let-7b might be an independent prognostic biomarker for glioma (P < .001, HR = 2.415; 95% CI: 1.531-3.808).Let-7b may be a promising prognostic factor in glioma.

Rashed WM, Hammad AM, Saad AM, Shohdy KS
MicroRNA as a diagnostic biomarker in childhood acute lymphoblastic leukemia; systematic review, meta-analysis and recommendations.
Crit Rev Oncol Hematol. 2019; 136:70-78 [PubMed] Related Publications
Several studies detected abnormal mi-RNAs expression levels in childhood Acute Lymphoblastic Leukemia (ALL) with potential diagnostic value. We conducted a systematic search on certain microRNAs in childhood ALL. We included 17 studies with a total of 928 ALL children and 307 controls. Ten studies provided miRNAs expression levels and seven provided frequency data. Sensitivity and specificity of a single miRNA ranged from 46.55% to 100% and from 71.8% to 100%, respectively. The highest diagnostic odds ratio (DOR) was for the diagnostic panel (miR-128a and miR-223) reaching 546 [95% CI: 73.768-4041.282]. Also, miR-128a, miR-128b, miR-223, let-7b, miR-155 and miR-24 can be used as diagnostic discriminatory biomarkers between ALL and AML. Further large cohort studies are needed to confirm our results.

Zhang J, Jiang Y, Han X, et al.
Differential expression profiles and functional analysis of plasma miRNAs associated with chronic myeloid leukemia phases.
Future Oncol. 2019; 15(7):763-776 [PubMed] Related Publications
AIM: This study was aimed to investigate the expression profiles and biological function of plasma miRNAs at different phases of chronic myeloid leukemia (CML).
MATERIALS & METHODS: Differentially expressed miRNAs were identified by microarray. The candidate miRNAs were validated by quantitative real-time PCR at chronic phase, accelerated phase and blast crisis. The functional analysis of miRNAs was carried out by using DAVID.
RESULTS: The putative targets of dysregulated miRNAs were involved in important signaling pathways. Plasma let-7b-5p and miR-451a expression was lower in CML patients, and plasma miR-451a gradually decreased from chronic phase to accelerated phase and blast crisis.
CONCLUSION: Dysregulated plasma miRNAs maybe play regulatory roles in pathogenesis of CML. Let-7b-5p and miR-451a can be used as potential biomarkers for the diagnosis and prognosis of CML.

Zhang Y, Zhang H, Kang H, et al.
Knockdown of long non-coding RNA HOST2 inhibits the proliferation of triple negative breast cancer via regulation of the let-7b/CDK6 axis.
Int J Mol Med. 2019; 43(2):1049-1057 [PubMed] Related Publications
The upregulation of long non‑coding RNA (lncRNA) human ovarian cancer‑specific transcript 2 (HOST2) has been identified in breast cancer. The present study aimed to investigate whether lncRNA HOST2 regulated the proliferation of triple negative breast cancer (TNBC) cells, and the underlying molecular mechanism. In total, 30 patients with primary TNBC, who were treated at Wuhai People's Hospital (Wuhai, China), were recruited for the present study. Reverse transcription‑quantitative polymerase chain reaction analysis was used for the examination of gene expression levels. A Cell Counting kit‑8 (CCK‑8) assay was used for the detection of cell proliferation. Phases of the cell cycle were evaluated by flow cytometry. Western blot analysis was performed to detect protein expression levels. A dual luciferase activity assay was performed to examine the interaction between microRNA (miRNA) and the 3' untranslated region (UTR) of target mRNA. The results revealed increased expression levels of HOST2 in tumor tissues from patients with TNBC. A positive correlation was identified between the expression of HOST2 and cyclin‑dependent kinase 6 (CDK6) in tumor tissues. The silencing of HOST2 induced cell proliferation inhibition and cell cycle redistribution in MDA‑MB‑231 and MDA‑MB‑468 TNBC cells. In these two cell lines, HOST2 silencing caused a decrease in the phosphorylation of RB1 and CDK6, which was observed at the mRNA and protein levels. However, the silencing of CDK6 did not alter the expression of HOST2. It was hypothesized and confirmed that let‑7b, a previously reported target miRNA of HOST2, was able to directly bind to the 3'UTR of CDK6 and repress its expression. The expression of let‑7b was negatively correlated with the expression of HOST2 and CDK6 in tumor tissues. Overall, the data suggested that lncRNA HOST2 acts as an oncogene in TNBC via the upregulation of CDK6.

Campayo M, Navarro A, Benítez JC, et al.
miR-21, miR-99b and miR-375 combination as predictive response signature for preoperative chemoradiotherapy in rectal cancer.
PLoS One. 2018; 13(11):e0206542 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer patients. Despite the benefits of CRT, its use in non-responder patients can be associated with increased toxicities and surgical resection delay. The identification of CRT response biomarkers, such as microRNAs, could improve the management of these patients. We have studied the microRNA expression in pretreatment endoscopy biopsies from rectal cancer patients treated with CRT to identify potential microRNAs able to predict CRT response and clinical outcome of these patients.
MATERIAL AND METHODS: RNA from pretreatment endoscopy biopsies from 96 rectal cancer patients treated with preoperative CRT were studied. Pathological response was graded according to the tumor regression grade (TRG) Dworak classification. In the screening phase, 377 miRNAs were studied in 12 patients with extreme responses (TRG0-1 vs TRG4). The potential role as predictive biomarkers for CRT response, disease-free survival (DFS) and overall survival (OS) of the miRNAs identified in the screening phase were validated in the whole cohort.
RESULTS: In the screening phase, an 8-miRNAs CRT-response signature was identified: let-7b, let-7e, miR-21, miR-99b, miR-183, miR-328, miR-375 and miR-483-5p. In the validation phase, miR-21, miR-99b and miR-375 emerged as CRT response-related miRNAs while miR-328 and let-7e emerged as prognostic markers for DFS and OS. Interestingly, ROC curve analysis showed that the combination of miR-21, miR-99b and miR-375 had the best capacity to distinguish patients with maximum response (TRG4) from others.
CONCLUSIONS: miR-21, miR-99b and miR-375 could add valuable information for individualizing treatment in locally advanced rectal cancer patients.

Oztemur Islakoglu Y, Noyan S, Aydos A, Gur Dedeoglu B
Meta-microRNA Biomarker Signatures to Classify Breast Cancer Subtypes.
OMICS. 2018; 22(11):709-716 [PubMed] Related Publications
Breast cancer is one of the leading causes of morbidity and mortality that is in need of novel diagnostics and therapeutics. Meta-analysis of microarray data offers promise to combine studies and provide more robust results. We report here a molecular classification of pathological subtypes (estrogen receptor [ER], progesterone receptor [PR], and Human Epidermal Growth Factor Receptor 2 [HER2]) of breast cancers with microRNA (miRNA)-dependent signatures. A ranking-based meta-analysis approach was applied to eight independent microarray data sets and meta-miRNA lists were obtained that are specific to each breast cancer subtype. The comparison of the lists with miRCancer and the PhenomiR 2.0 databases pointed out nine prominent miRNAs: let-7b-5p, let-7c-5p, let-7e-5p, miR-130a-3p, miR-30a-5p, miR-92a-1-5p, miR-211-5p, miR-500a-3p, and miR-516b-3p. Further analysis conducted with the TCGA data showed that these miRNAs can differentiate tumors from normal samples as well as discriminate the molecular subtypes of breast cancer. According to the PAM50 classification, three of these miRNAs (let-7b-5p, let-7c-5p, and miR-30a-5p) downregulated significantly, whereas miR-130a-3p, miR-92a-1-5p, miR-211-5p, and miR-500a-3p upregulated in tumors from the luminal A to the basal-like subtypes. When the prominent meta-miRNAs and their targets were analyzed, they appeared to be taking part in important signaling pathways in cancer such as the PI3K-Akt signaling and the p53 signaling pathways. Furthermore, the regulatory genes, which are key players for ER, PR, and ErBb signaling pathways, were found to be under control of several meta-miRNAs. These meta-miRNAs and the genes they are regulating offer new promise for future translational research and potential targets for precision medicine diagnostics.

Guo X, Han T, Hu P, et al.
Five microRNAs in serum as potential biomarkers for prostate cancer risk assessment and therapeutic intervention.
Int Urol Nephrol. 2018; 50(12):2193-2200 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prostate cancer (PCa) is a common malignant human tumor and one of the main causes of cancer-related deaths in men. At present, prostate-specific antigen levels are widely used to diagnose PCa in the clinic, but they are not sufficient for an accurate early diagnosis or prognosis.
METHODS: To identify potential molecular markers for PCa, we used real-time PCR to measure the expression levels of various microRNAs, including miR-1825, miR-484, miR-205, miR-141, and let-7b, in the serum of 72 PCa patients and 34 healthy controls.
RESULTS: miR-1825, miR-484, miR-205, miR-141, and let-7b were shown to be highly specific for PCa, suggesting that they could be used as PCa tumor screening biomarkers. miR-205 may also be used as a biomarker for indicating bone metastasis in PCa patients, miR-1825 levels may help indicate tumor-node-metastasis classification, the evaluation of treatment effects, and determining prognosis, while let-7b levels may indicate potential tumor malignancy and the hormone resistance status and could be used as a basis to adjust individual treatments for the high-risk, early diagnosis of refractory PCa.
CONCLUSION: This study identified possible PCa tumor markers to more accurately predict the occurrence, progression, and prognosis of PCa, and which could be used in the development of tumor drug therapy.

Han X, Zhang JJ, Han ZQ, et al.
Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB.
Cancer Gene Ther. 2018; 25(11-12):300-308 [PubMed] Related Publications
Platinum-based chemotherapy is currently a standard treatment strategy for patients with gastric cancer. Eventhough it has been widely shown that microRNAs (miRNAs) are involved in tumor development, whether miRNAs have a role in chemosensitivity of gastric cancer cells to platinum-based treatment remain largely undefined. In this study, a cisplatin-resistant gastric cancer cell line (SGC7901/DDP) with stable enhanced expression or knockdown of let-7b was generated. MTT and TUNEL assays were carried out to assess whether miR-let-7 is crucial for cell viability and apoptosis, respectively. In vitro luciferase reporter assay was performed to explore target genes of let-7b. Further, a subcutaneously transplanted tumor model in BALB/c nude mice was used to determine the impacts of let-7b on tumor growth in vivo. We observed that the let-7b-expression level of SGC7901/DDP cells was significantly lower than for its parental SGC7901 cells. Transfection of let-7b mimics was found to increase the cytotoxicity of DDP to SGC7901/DDP cells by inducing apoptosis. However, reversed cytotoxicity of DDP was observed in SGC7901/DDP cells with knockdown of let-7b. Luciferase reporter assay indicated that let-7b targeted AURKB in SGC7901/DDP cells. Knockdown of AURKB imitated the effect of let-7b overexpression on the sensitivity of SGC7901/DDP cells to DDP. Further investigation demonstrated that the SGC7901/DDP primary tumor growth was significantly reduced by let-7b mimic transfection. These findings indicate that overexpression of let-7b might provide a potential strategic approach for attenuating DDP resistance in SGC7901/DDP human gastric cancer cells.

Shafik RE, Abd El Wahab N, Senoun SA, et al.
Expression of Micro-RNA 128 and Let-7b in Pediatric Acute Lymphoblastic Leukemia Cases
Asian Pac J Cancer Prev. 2018; 19(8):2263-2267 [PubMed] Free Access to Full Article Related Publications
Background: MicroRNAs (miRNAs) play important roles in the pathogenesis of leukemia and their altered expression is associated with many types of solid and hematological malignancies. Methods: The study was performed on 70 consecutive newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients, of which 56 were evaluated for both bone marrow miR-128 and let-7b (all 70 for let-7b) by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). In addition, seven age and sex matched healthy controls were assessed. Results: miR-128 expression was significantly higher in ALL patients compared with healthy controls (p<0.001). However, the expression levels of let-7b showed no statistical significant difference between the groups. No significant links were noted with clinical details, laboratory data and response to treatment. Conclusion: The results suggest that determination of miR-128 expression level may provide a tool for confirmation of a diagnosis of childhood ALL, follow up for response of treatment and a possible predictor of early relapse. Any role of let-7b in pediatric ALL needs to be further assessed.

Yang C, Li B, Yu J, et al.
Ultrasound microbubbles mediated miR-let-7b delivery into CD133
Biosci Rep. 2018; 38(5) [PubMed] Free Access to Full Article Related Publications
Ovarian cancer stem cells (OCSCs) are considered the reason for ovarian cancer's emergence and recurrence. Ultrasound-targetted microbubble destruction (UTMD), a non-vial, safe, and promising delivery method for miRNA, is reported to transfect cancer stem cells (CSCs). In the present study, we investigated to transfect miR-let-7b into OCSCs using UTMD. The CD133

Xu X, Bao Z, Liu Y, et al.
PBX3/MEK/ERK1/2/LIN28/let-7b positive feedback loop enhances mesenchymal phenotype to promote glioblastoma migration and invasion.
J Exp Clin Cancer Res. 2018; 37(1):158 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Brain invasion by glioblastoma (GBM) determines recurrence and prognosis in patients, which is, in part, attributed to increased mesenchymal transition. Here, we report evidence favoring such a role for the Pre-B-cell leukemia homebox (PBX) family member PBX3.
METHODS: Western blot, immunohistochemistry, qRT-PCR and datasets mining were used to determined proteins or genes expression levels. Wound-healing and transwell assays were used to examine the invasive abilities of GBM cells. Dual-luciferase reporter assays were used to determine how let-7b regulates PBX3. Chromatin-immunoprecipitation (ChIP) and rescue experiments were performed to investigate the involved molecular mechanisms. Orthotopic mouse models were used to assess the role of PBX3 in vivo.
RESULTS: We found that PBX3 expression levels positively correlated with glioma mesenchymal markers. Ectopic expression of PBX3 promoted invasive phenotypes and triggered the expression of mesenchymal markers, whereas depletion of PBX3 reduced GBM cell invasive abilities and decreased the expression of mesenchymal markers. In addition, inhibition of PBX3 attenuated transforming growth factor-β (TGFβ)-induced GBM mesenchymal transition. Mechanistic studies revealed that PBX3 mediated GBM mesenchymal transition through activation of MEK/ERK1/2, leading to increased expression of LIN28 by c-myc. Increased LIN28 inhibited let-7b biogenesis, which then promoted the pro-invasive genes, such as HMGA2 and IL-6. Furthermore, let-7b suppressed PBX3 by directly targeting 3'-UTR of PBX3. Thus, repressed let-7b by PBX3 amplifies PBX3 signaling and forms a positive feedback loop to promote GBM mesenchymal transition.
CONCLUSIONS: These data highlight the importance of PBX3 as a key driver of mesenchymal transition and potential therapeutic target.

He Z, Deng W, Jiang B, et al.
Hsa-let-7b inhibits cell proliferation by targeting PLK1 in HCC.
Gene. 2018; 673:46-55 [PubMed] Related Publications
Previous studies have shown that high levels of PLK1 are expressed in HCC, and PLK1 inhibitors are being tested in clinical trials. However, the mechanisms, which regulate PLK1 expression in HCC, have not been clarified. Here, we show that induction of let-7b over-expression inhibits the PLK1-regulated luciferase activity in HEK-293T cells, and decreases the levels of PLK1 expression in HCC cells. Furthermore, the levels of let-7b expression were negatively correlated with PLK1 expression in HCC tissues. Let-7b over-expression inhibited the proliferation of HCC cells and promoted their apoptosis, which were partially rescued by increased PLK1 expression. Let-7b over-expression decreased the levels of PLK1, CDC25C and Survivin phosphorylation and CDC2, β-catenin, TCF-4 expression, which were mitigated by increased PLK1 expression in MHCC-97H cells. Let-7b over-expression inhibited the development and growth of implanted HCC tumors in mice by decreasing PLK1 and Survivin expression in the tumors. Together, our data indicated that let-7b targeted PLK1 to inhibit HCC growth and induce their apoptosis by attenuating the PLK1-mediated Survivin phosphorylation. Our findings may provide new insights into the pathogenesis of HCC.

Sun J, Li Y, Chen C, et al.
Magnetic Ni/Fe layered double hydroxide nanosheets as enhancer for DNA hairpin sensitive detection of miRNA.
Talanta. 2018; 187:265-271 [PubMed] Related Publications
A new non-enzyme method based on hybridization chain reaction (HCR) and colorimetric reaction catalyzed by magnetic Ni/Fe layered double hydroxide (LDH) nanosheets was developed for detection of microRNA (miRNA), let-7b. The DNA hairpins from HCR were separated and adsorbed by Ni/Fe LDH. The peroxidase-like activity of Ni/Fe LDH was found to be enhanced by the DNA hairpins on the surface. The factors, such as ratio of Ni/Fe and concentration of DNA hairpins, related to the catalytic activity were evaluated and the mechanism was discussed. The results of this new detection method for let-7b provided low limit of detection (0.36 fM), wide linear range (0.01 pM to 200 pM) with good linearity (r

Zedan AH, Hansen TF, Assenholt J, et al.
microRNA expression in tumour tissue and plasma in patients with newly diagnosed metastatic prostate cancer.
Tumour Biol. 2018; 40(5):1010428318775864 [PubMed] Related Publications
Prostate cancer is the most common cancer among men in the western world. Clinical practice is continuously challenged by the pitfalls of the available diagnostic tools. microRNAs may represent promising biomarkers in many types of human cancers, including prostate cancer. The aim of this study was to investigate microRNA expression in tumour tissue and matched plasma in a cohort of patients with primary metastatic prostate cancer. The relative expression of 12 microRNAs was assessed in diagnostic needle biopsies from the prostate and matched plasma samples in two prospective cohorts (screening cohorts) comprising 21 patients with metastatic prostate cancer and 25 control patients. An independent validation cohort of plasma samples was collected prospectively from 149 newly diagnosed patients with local/locally advanced prostate cancer. Analyses were performed using real-time polymerase chain reaction. miRNA-93 showed a significant negative correlation between expression in tumour tissue and plasma in patients with metastatic prostate cancer. Furthermore, the plasma level of miRNA-93 significantly decreased after treatment in patients with local/locally advanced prostate cancer compared to baseline plasma level. The expression of six microRNAs (let-7b, miRNA-34a, -125b, -143, -145 and -221) was downregulated, and three microRNAs (miRNA-21, -25 and miRNA-93) were upregulated in tumour tissue compared to benign prostate tissue. In plasma, six microRNAs were upregulated (miRNA-21, -125b, -126, -141, -143 and -375), while let-7b was downregulated in patients with metastatic prostate cancer compared to the control cohort. In the metastatic prostate cancer cohort, the expression of four microRNAs (miRNA-125b, -126, -143 and -221), and miRNA-141 in tissue was associated with Gleason score and prostate-specific antigen, respectively. The expression of miRNA-93 in tumour tissue was correlated with matched plasma levels and showed a significant decrease in plasma level after intervention in local prostate cancer. Differential expression between tumour and benign prostate was detected for several microRNAs in both tissue and plasma.

Lou Y, Jiang H, Cui Z, et al.
Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high‑grade ovarian serous cancer.
Int J Mol Med. 2018; 42(1):91-104 [PubMed] Free Access to Full Article Related Publications
High‑grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high‑grade ovarian serous cancer progression and prognosis are urgently required. Long non‑coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various cancers, including HOX transcript antisense RNA, competing endogenous lncRNA 2 for microRNA let‑7b, urothelial cancer associated 1, and H19, imprinted maternally expressed transcript (non‑protein coding). However, few studies have investigated the differential expression of lncRNAs in high‑grade ovarian serous cancer. In the present study, differences in lncRNA and mRNA expression profiles between high‑grade ovarian serous cancer tissue samples and healthy fallopian tube tissue samples were investigated using microarray analysis, and the differential expression of lncRNAs and mRNAs was confirmed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Then, five abnormally expressed lncRNAs were selected, and the associations between these lncRNAs and ovarian cancer clinicopathological parameters were examined using RT‑qPCR. The expression profiles of certain lncRNAs and mRNAs were confirmed to be altered between high‑grade ovarian serous cancer tissues and healthy fallopian tube tissues. Furthermore, the expression levels of selected lncRNAs were associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore be involved in the pathogenesis of high‑grade ovarian serous cancer. The results of the present study provide an experimental foundation for further exploration of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of high‑grade ovarian serous cancer.

Yamamoto CM, Oakes ML, Murakami T, et al.
Comparison of benign peritoneal fluid- and ovarian cancer ascites-derived extracellular vesicle RNA biomarkers.
J Ovarian Res. 2018; 11(1):20 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Extracellular vesicles (EVs) are considered as a new class of resources for potential biomarkers. We analyzed expression of specific mRNA and miRNA in EVs derived from ovarian cancer ascites and the ideal controls, peritoneal fluids from benign patients for potential early detection and prognostic biomarkers.
METHODS: Fluids were collected from subjects with benign cysts or endometrioma (n = 10), or low/high grade serous ovarian carcinoma (n = 8). EV particles were captured using primarily ExoComplete filterplate or ultracentrifugation and analyzed by nanoparticle tracking analysis, ELISA, and scanning electron microscopy. EV RNAs extracted from two ascites and three peritoneal fluids were submitted for next-generation sequencing. The expression of 34 mRNA and 18 miRNAs in the EVs isolated from patient fluids and cell line media was determined using qPCR.
RESULTS: EVs isolated from patient samples had concentrations greater than 10
CONCLUSIONS: This study indicates that EV mRNA profiles can reflect the disease stage and may provide a potentially novel source for discovery of biomarkers in ovarian cancer.

Liu Z, Tian Y, Jiang Y, et al.
Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction.
Cell Physiol Biochem. 2018; 45(1):343-355 [PubMed] Related Publications
BACKGROUND/AIMS: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction.
METHODS: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot.
RESULTS: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function.
CONCLUSION: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

Ling R, Zhou Y, Zhou L, et al.
Lin28/microRNA-let-7a promotes metastasis under circumstances of hyperactive Wnt signaling in esophageal squamous cell carcinoma.
Mol Med Rep. 2018; 17(4):5265-5271 [PubMed] Free Access to Full Article Related Publications
Dysregulation of micro (mi)RNA-let-7 has been associated with the development and prognosis of multiple cancer types. Lin28, a RNA-binding protein, plays a conserved role in regulating the maturation of let-7 family proteins. However, few studies have focused on the effects of Lin28/let-7 on Wnt-activated esophageal squamous cell carcinoma (ESCC). Analysis of the expression of let-7a, let-7b and let-7c in clinical tissues revealed that lower let-7a expression was correlated with higher tumor node metastasis staging and recurrence in patients with ESCC. Furthermore, it was demonstrated that let-7a was inversely correlated with the migration and invasion of ESCC cells. In addition, epithelial-mesenchymal transition, and the expression of VEGF-C and MMP9 were effectively decreased by let-7a-mimic or siRNA-Lin28 pretreatment. Mechanistically, Lin28 functioned as the key factor in signal transduction, which regulated the expression of let-7a and the downstream genes along the Wnt signaling pathway. Taken together, these findings identified a biochemical and functional association between Lin28/let-7a, and the Wnt pathway in ESCC cells.

Lu PW, Li L, Wang F, Gu YT
Effects of long non-coding RNA HOST2 on cell migration and invasion by regulating MicroRNA let-7b in breast cancer.
J Cell Biochem. 2018; 119(6):4570-4580 [PubMed] Related Publications
The study intends to investigate the effects of long non-coding RNA HOST2 (lncRNA HOST2) on cell migration and invasion by regulating microRNA let-7b (let-7b) in breast cancer. Breast cancer and adjacent normal tissues were collected from 98 patients with breast cancer. Breast cancer MCF-7 cells were divided into the blank, negative control (NC), pcDNA3-Mock, siHOST2, let-7b inhibitor, pcDNA3-HOST2, let-7b mimic, pcDNA3-HOST2 + let-7b mimic, and siHOST2 + let-7b inhibitor groups. RT-qPCR was used to detect the mRNA expressions of HOST2, let-7b, and c-Myc. Western blotting was conducted to measure the c-Myc expression. Scratch test and Transwell assay were applied to detect the cell motility, migration, and invasion. Xenograft tumor in nude mice was performed to evaluate the effect of different transfection on the tumor growth. Compared with adjacent normal tissues, HOST2 expression was higher but let-7b expression lower in breast cancer tissues. HOST2 expression in breast cancer cells was remarkably increased compared with that in the normal breast epithelial MCF-10A cells. In MCF-7 cells, in comparison with the blank and NC groups, expressions of HOST2 and c-Myc were reduced, but let-7b expression was remarkably elevated in the siHOST2 and let-7b mimic groups; the let-7b inhibitor group exhibited higher expressions of HOST2 and c-Myc but lower let-7b expression. Overexpression of HOST2 could promote cell motility, migration and invasion, thus enhancing the growth of breast cancer tumor. By inhibiting HOST2, opposite trends were found. LncRNA HOST2 promotes cell migration and invasion by inhibiting let-7b in breast cancer patients.

Zhang C, Xiao X, Chen M, et al.
Liver kinase B1 restoration promotes exosome secretion and motility of lung cancer cells.
Oncol Rep. 2018; 39(1):376-382 [PubMed] Free Access to Full Article Related Publications
Liver kinase B1 (LKB1) regulates a variety of cellular functions, including cell polarity, energy metabolism and cell growth, by targeting multiple signaling pathways such as AMPK/mTOR and p53. LKB1 functions as a tumor suppressor in sporadic cancers including lung cancer. Extracellular vesicles such as exosomes secreted by cancer cells modulate the tumor microenvironment and progression by targeting both tumor cells (autocrine actions) and other types of cells associated with tumors (paracrine actions). While the roles of LKB1 in cellular signaling in general is well-studied, its specific role in exosome-mediated signaling remains to be explored. To this purpose, we reintroduced LKB1 into H460 and A549 lung cancer cells that are endogenously deficient in LKB1 expression. Notably, we found that while restoration of LKB1 significantly reduced lung cancer cell growth as expected, it greatly promoted cell motility and enhanced the release of exosomes. In addition, exosomes isolated from H460 cells with stable restoration of LKB1 had much higher ability in stimulating lung cancer cell migration than did those from H460 cells lacking LKB1. Mechanistically, restoration of LKB1 in H460 cells inhibited cellular expression and exosomal secretion of migration-suppressing microRNAs (miRNAs), including miR-125a, miR-126 and let7b. Taken together, the present study revealed a new role for LKB1 in promoting cell motility by downregulating migration-suppressing miRNA expression and exosome secretion.

Zhang J, Raju GS, Chang DW, et al.
Global and targeted circulating microRNA profiling of colorectal adenoma and colorectal cancer.
Cancer. 2018; 124(4):785-796 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell-free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma.
METHODS: The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays.
RESULTS: The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR-17-5p/miR-135b, miR-92a-3p/miR135b, and miR-451a/miR-491-5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let-7b/miR-367-3p, miR-130a-3p/miR-409-3p, miR-148-3p/miR-27b, miR-148a-3p/miR-409-3p, and miR-21-5p/miR-367-3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism-related and inflammation-related pathways.
CONCLUSIONS: The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785-96. © 2017 American Cancer Society.

Li H, Zhao L, Zhang Z, et al.
Roles of microRNA let-7b in papillary thyroid carcinoma by regulating HMGA2.
Tumour Biol. 2017; 39(10):1010428317719274 [PubMed] Related Publications
The incidence of thyroid cancer has increased significantly in the last decade, and the most frequent type of this cancer is papillary thyroid carcinoma. MicroRNAs have been demonstrated to be abnormally expressed in tumors and associated with the development of the tumors. Our aim was to analyze the role and molecular mechanisms of tumor suppressor let-7b in the papillary thyroid carcinoma. Expression of let-7b and high-mobility group A2 in papillary thyroid carcinoma tissues and cell lines was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis. To explore the role of let-7b or high-mobility group A2 in the BCPAP and TPC-1 cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods were used. Let-7b expression was significantly downregulated while expression of high-mobility group A2 was upregulated dramatically in papillary thyroid carcinoma tissues and cells compared with that in normal thyroid tissues and cells. In addition, overexpression of let-7b or knockdown of high-mobility group A2 inhibited cell migration and invasion compared with that of control. Besides, high-mobility group A2 was negatively regulated by let-7b in BCPAP cells. Moreover, high-mobility group A2 reintroduction reversed the anti-proliferation, anti-migration, and anti-invasion roles of let-7b. Let-7b might function as a tumor suppressor in papillary thyroid carcinoma by suppressing the expression of high-mobility group A2, and therefore might provide a promising therapeutic target for patients with papillary thyroid carcinoma.

Di Fazio P, Maass M, Roth S, et al.
Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung.
Tumour Biol. 2017; 39(10):1010428317728417 [PubMed] Related Publications
Typical and atypical carcinoid tumors belong to the neuroendocrine lung tumors. They have low recurrence and proliferation rate, lymph node, and distant metastases. Nevertheless, these tumors have shown a more aggressive behavior. In the last years, microRNAs were screened as new tumor markers for their potential diagnostic and therapeutic relevance. The expression of hsa-let-7b-5p, hsa-let-7f-5p, hsa-miR-222-3p, and their targets HMGA2 (high-mobility group A2) and CDKN1B (cyclin-dependent kynase inhibitor 1B, p27

Pang Y, Liu J, Li X, et al.
Nano Let‑7b sensitization of eliminating esophageal cancer stem‑like cells is dependent on blockade of Wnt activation of symmetric division.
Int J Oncol. 2017; 51(4):1077-1088 [PubMed] Free Access to Full Article Related Publications
The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence. Higher ratios of cancer stem cells indicated later clinical stages, and Wnt signaling activation was more frequent in later esophageal carcinoma. Further in bench studies, we explored the suppressive roles and the mechanisms involved in Let‑7 on self-renewal in ECA‑109 and ECA‑9706 esophageal cancer stem cells. Isolated cancer stem cells naturally divide symmetrically and are therapy resistant. Therapy of fluorouracil and docetaxel both enriched the stem cells, proving the resistant characteristics of cancer stem cells. Wnt activation stimulated more symmetric division of stem cells, resulting in self-renewal promotion, which could be blocked by Let‑7 overexpression. Furthermore, enforced Let‑7 sensitized the stem cells to chemotherapies in a Wnt pathway inhibition-dependent manner, contributing to Let‑7 sensitization of chemotherapeutic response. Wnt activation weakened the suppressive Let‑7b through the sponge functions of CCAT-1, forming the negative feedback loop of Let‑7b/Wnt/CCAT1. These results identified the crucial participation of stem cells in esophageal cancer occurrence and progression as the potent indicator, and also indicate the potential powerful agent of Let‑7 nano-particles in treatment of cancer.

Fedorko M, Juracek J, Stanik M, et al.
Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma.
Biochem Med (Zagreb). 2017; 27(2):411-417 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls.
MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach.
RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%).
CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.

Greither T, Vorwerk F, Kappler M, et al.
Salivary miR-93 and miR-200a as post-radiotherapy biomarkers in head and neck squamous cell carcinoma.
Oncol Rep. 2017; 38(2):1268-1275 [PubMed] Related Publications
Head and neck squamous cell carcinoma is the 6th most malignant tumor entity worldwide and has exhibited a 5-year mortality of approximately 50% for the last fifty years. For the therapy monitoring and successful management of this tumor entity new and easily accessible biomarkers are greatly needed. The aim of the study was to determine whether and to what extent microRNAs, a class of small regulatory RNAs, are detectable in saliva post-radiation therapy. The expression and feasibility as therapy monitoring marker of the microRNAs were analyzed by RT-qPCR in 83 saliva samples from 33 patients collected at several time points pre-, during and post-radiotherapy treatment. Ten head and neck squamous cell carcinoma- or radiation-associated microRNAs (miR-93, miR-125a, miR-142-3p, miR-200a, miR-203, miR-213, let-7a, let-7b, let-7g and let-7i) were analyzed. All were detectable to a different extent in the saliva of the patients. miR-93 and miR-200a were significantly higher expressed 12 months post-radiotherapy than at baseline (p=0.047 and p=0.036). These results point towards miR-93 and miR-200a as biomarkers for the treatment monitoring post-radiation of head and neck squamous cell carcinoma.

Zhang Z, Lu J, Guo G, et al.
IKBKE promotes glioblastoma progression by establishing the regulatory feedback loop of IKBKE/YAP1/miR-Let-7b/i.
Tumour Biol. 2017; 39(7):1010428317705575 [PubMed] Related Publications
Recently, we have demonstrated that IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) is overexpressed in human glioblastoma and that inhibition of IKBKE remarkably suppresses the proliferative and invasive behaviour of glioblastoma cells. However, the specific pathogenic molecular mechanism remains to be elucidated. In this study, we verified that IKBKE promotes YAP1 expression via posttranslational modification and accelerates YAP1 translocation to the nucleus for the development of glioblastoma. We then determined that YAP1 negatively regulates miR-let-7b/i by overexpressing and silencing YAP1 expression. In addition, miR-let-7b/i feedback decreases the expression of IKBKE and YAP1 and suppresses the transportation of YAP1 located in the nucleus. Therefore, the regulatory feedback circuit of IKBKE↑→YAP1↑→miR-let-7b/i↓→IKBKE↑ dictates glioblastoma progression. Thus, we propose that blocking the circuit may be a new therapeutic strategy for the treatment of glioblastoma.

Cai H, Chen Y, Yang X, et al.
Let7b modulates the Wnt/β-catenin pathway in liver cancer cells via downregulated Frizzled4.
Tumour Biol. 2017; 39(7):1010428317716076 [PubMed] Related Publications
Let7 microRNA implicated in many cellular processes and participated in the progress of various tumors. Similarly, Wnt signaling pathway plays an important role in morphogenesis, differentiation, cell survival, and proliferation. However, there is little research focusing on the relevance between Let7b and Wnt/β-catenin signaling pathway, especially in liver cancer cell. To study this, human liver cancer cells HUH7 and MHCC97H were cultured, enhanced, or inhibited the expression of Let7b in two cell lines. Western blotting was used to measure the expression of Wnt signaling-related protein β-catenin and Frizzled family receptor. CD24

Zhou W, Ye XL, Xu J, et al.
The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b.
Sci Signal. 2017; 10(483) [PubMed] Related Publications
Metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. The pathophysiological course of metastasis is mediated by the dynamic plasticity of cancer cells, which enables them to shift between epithelial and mesenchymal phenotypes through a transcriptionally regulated program termed epithelial-to-mesenchymal transition (EMT) and its reverse process, mesenchymal-to-epithelial transition (MET). Using a mouse model of spontaneous metastatic breast cancer, we investigated the molecular mediators of metastatic competence within a heterogeneous primary tumor and how these cells then manipulated their epithelial-mesenchymal plasticity during the metastatic process. We isolated cells from the primary mammary tumor, the circulation, and metastatic lesions in the lung in TA2 mice and found that the long noncoding RNA (lncRNA) H19 mediated EMT and MET by differentially acting as a sponge for the microRNAs miR-200b/c and let-7b. We found that this ability enabled H19 to modulate the expression of the microRNA targets

Spolverini A, Fuchs G, Bublik DR, Oren M
let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery.
Oncogene. 2017; 36(42):5819-5828 [PubMed] Free Access to Full Article Related Publications
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer. We now report that let-7b and let-7c can positively regulate cellular H2Bub1 levels. Overexpression of let-7b and let-7c in a variety of non-transformed and cancer-derived cell lines results in H2Bub1 elevation. The positive effect of let-7b and let-7c on H2Bub1 levels is achieved through targeting of multiple mRNAs, coding for distinct components of the H2B deubiquitylation machinery. Specifically, let-7b and let-7c bind directly and inhibit the mRNAs encoding the DUBs USP42 and USP44, and also the mRNA encoding the adapter protein ATXN7L3, which is part of the DUB module of the SAGA complex. RNF20 knockdown (KD) strongly reduces H2Bub1 levels and increases the migration of non-transformed mammary epithelial cells and breast cancer-derived cells. Remarkably, overexpression of let-7b, which partly counteracts the effect of RNF20 KD on H2Bub1 levels, also reverses the pro-migratory effect of RNF20 KD. Likewise, ATXN7L3 KD also increases H2Bub1 levels and reduces cell migration, and this anti-migratory effect is abolished by simultaneous KD of RNF20. Together, our findings uncover a novel function of let-7 miRNAs as regulators of H2B ubiquitylation, suggesting an additional mechanism whereby these miRNAs can exert their tumor-suppressive effects.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. microRNA let-7b, Cancer Genetics Web: http://www.cancer-genetics.org/MIRLET7B.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 29 August, 2019     Cancer Genetics Web, Established 1999