Abstract
BackgroundMicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). Previous study has suggested the important regulation function of miR-10b in ccRCC. However, the direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed.MethodsmiR-10b and HOXA3 was detected by qRT-PCR. MTT, colony formation assay, wound-healing and transwell assays were performed to detect cell proliferation, colony formation, migration, and invasion abilities in ccRCC. Western blot analyses were performed to evaluate the protein expression of HOXA3, YAP, FAK and MMP-9. Dual luciferase reporter assay was employed to measure potential molecular mechanism of miR-10b in ccRCC.ResultsmiR-10b was down-regulated in 786-O and A498 cells as compared to renal tubular HK-2 cells. By contrast, HOXA3 and YAP was up-regulated in ccRCC cells and tissues. Functionally, knockdown of YAP inhibited cell proliferation, migration and invasion. Knockdown of FAK downregulated YAP, in turn, resulted in a decrease of HOXA3 expression. Mechanically, miR-10b targets HOXA3 to exert its tumor-suppressive effect on ccRCC in vitro.ConclusionsThese novel data suggest that miR-10b suppresses cell invasion and metastasis through targeting HOXA3, which partially passed through the FAK/YAP signaling pathway.
Highlights
Clear cell renal cell carcinoma is the most common type of RCC, responsible for approximately 75–80% of cases
We demonstrated that miR-10b, through targeting HOXA3 regulated by Focal adhesion kinase (FAK)/ Yes-associated protein (YAP) signaling pathway, suppresses cell invasion and metastasis of clear-cell renal cell carcinoma (ccRCC)
Results miR-10b was down-regulated and HOXA3 and YAP were up-regulated in ccRCC cells Given that miR-10b is a negative regulator of ccRCC cell metastasis, we first detected the miR-10b expression level in ccRCC cell lines, CAKI cells, as well as HE-2 cells
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common type of RCC, responsible for approximately 75–80% of cases. It is the second leading cause of death from urologic malignancies, which is characterized by extraordinarily high rates of local invasion, malignancy, and mortality, and resistance to chemotherapy and radiotherapy [1,2,3,4]. MicroRNA-10b (miR-10b) has been suggested to be dys-regulated in a number of cancers and to act as a key regulator of cell invasion and metastasis [10]. MicroRNAs have been related to tumor progression in diverse human cancers including clear-cell renal cell carcinoma (ccRCC). The direct target of miR-10b in ccRCC and the related molecular mechanisms has not yet been revealed
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