miR-10b is overexpressed in hepatocellular carcinoma and promotes cell proliferation, migration and invasion through RhoC, uPAR and MMPs

Abstract. MicroRNAs are deregulated in numerous types of human cancers and have crucial roles in the carcinogenesis and progression of human cancers. MicroRNA-10b (miR-10b) has been studied in several types of human cancer. However, the expression and roles of miR-10b in cervical cancer remain unknown. In the present study, the expression, functions and molecular mechanisms of miR-10b were explored in cervical cancer. The present data revealed that miR-10b was significantly downregulated in cervical cancer tissues and cell lines. In addition, miR-10b overexpression inhibited the proliferation, migration and invasion of cervical cancer cells, while miR-10b under-expression had the opposite effect. Based on bioinformatics analysis, a luciferase reporter assay and western blot analysis, insulin-like growth factor-1 receptor (IGF-1R) was identified as a direct target of miR-10b in cervical cancer. In addition, IGF-1R small interfering RNA-mediated knockdown of IGF-1R also inhibited the proliferation, migration and invasion of the cervical cancer cells. In conclusion, the present study demonstrated that miR-10b serves an important role in cervical cancer progression by targeting IGF-1R.

The invasive and metastatic properties of many human tumors have been associated with upregulation of the microRNA miR-10b, but its functional contributions in this setting have not been fully unraveled. Here we report the generation of miR-10b-deficient mice in which miR-10b is shown to be largely dispensable for normal development but critical to tumorigenesis. Loss of miR-10b delays oncogene-induced mammary tumorigenesis and suppresses epithelial-mesenchymal transition, intravasation, and metastasis in a mouse model of metastatic breast cancer. Among the target genes of miR-10b, the tumor suppressor genes Tbx5 and Pten and the metastasis suppressor gene Hoxd10 are significantly upregulated by miR-10b deletion. Mechanistically, miR-10b promotes breast cancer cell proliferation, migration, and invasion through inhibition of the expression of the transcription factor TBX5, leading to repression of the tumor suppressor genes DYRK1A and PTEN. In clinical specimens of breast cancer, the expression of TBX5, HOXD10, and DYRK1A correlates with relapse-free survival and overall survival outcomes in patients. Our results establish miR-10b as an oncomiR that drives metastasis, termed a metastamiR, and define the set of critical tumor suppressor mechanisms it overcomes to drive breast cancer progression.

Background/Aims: Adenomyosis is a disease in which ectopic endometrial glands and stromal cells appear in the uterine myometrium. Despite its prevalence, the molecular mechanisms involved in the development of adenomyosis are largely unknown. The aim of this study was to investigate the role of miR-10b and its target genes ZEB1 and PIK3CA in adenomyosis. Methods: 1387 miRNAs in human normal endometrium and ectopic endometrial lesions of adenomyosis using a microarray screen assay. The significant differential expression of 10 miRNAs was confirmed by qRT-PCR. The expression of miR-10b in endometrial epithelial cells isolated from normal endometrium and paired eutopic and ectopic endometrium of adenomyosis was measured by qRT-PCR. Subsequently, the targets of miR-10b were predicted by bioinformatics and confirmed using a luciferase assay, and the mRNA and protein expression of ZEB1 and PIK3CA were assessed in the endometrium or endometrial epithelial cells by qRT-PCR and western blotting or immunohistochemical analysis. Cell migration and cell invasion of endometrial epithelial cells with different treatments by Transwell assays. The expression of p-AKT, Akt and E-cadherin proteins was determined by Western blot analysis. Results: MiR-10b expression was significantly downregulated in both adenomyotic lesions and adenomyotic epithelial cells. MiR-10b overexpression in adenomyotic epithelial cells inhibited cell migration and invasion. We then demonstrated that miR-10b directly targets the 3'-UTRs of ZEB1 and PIK3CA, and downregulates ZEB1 and PIK3CA in adenomyotic epithelial cells, leading to increased E-cadherin expression and decreased Akt phosphorylation. Conclusions: miR-10b directly targets ZEB1 and PIK3CA to curb adenomyotic epithelial cell invasiveness via upregulation of E-Cadherin and inhibition of Akt phosphorylation.