MiRNA-148a inhibits cell growth and drug resistance by regulating WNT10a expression in renal cell carcinoma.

Abstract

BackgroundWe aimed to explore miR-148a exerts a tumor suppressor effect and arsenic trioxide (As2O3) sensitivity on renal cell carcinoma (RCC).MethodsWe performed polymerase chain reaction (PCR) on 42 pairs of tumor and paracancerous samples collected from RCC patients to investigate the miR-148a expression; meanwhile, we analyzed the interplay between clinical indicators and miR-148a expression of RCC. Then, the influence of miR-148a overexpression on the functions of RCC cells were analyze using transwell migration assay, Cell Counting Kit-8 (CCK-8), and cell wound healing assay. Furthermore, the ability of miR-148a to sensitize Caki-1 cells treated with As2O3 were detected using flow cytometry. Finally, the relevant mechanism of miR-148a on the downstream gene Wnt family member 10A (WNT10a) was explored by cell reverse method.ResultsThe results from RCC patients indicated a significantly lower miR-148a level than adjacent tissues. The low miR-148a expression increased prevalence of distant metastasis and decreased survival rate compared to those with high expression in patients. In the RCC cell lines, the proliferation and metastasis ability of the miR-148a mimic group was remarkably lower than the miR-NC group. At the same time, it was verified that WNT10a was remarkably higher cell lines and RCC tissues; and negatively related to miR-148a expression. In addition, miR-148a mimics were found to remarkably reduce the protein expression of WNT10a. In the cell reverse experiment, overexpression of WNT10a was confirmed to offset the miR-148a mimics effect on metastasis and proliferation of RCC cells. In addition, an increase in relative apoptosis was detected in As2O3 treated with/without miR-148a mimics for 48 hours, and apoptosis was significantly reduced after transfection with WNT10a in the Caki-1 cell line and significantly reduced after combined treatment.ConclusionsThe study revealed that miR-148a is associated with distant metastases and leads to poor prognosis in RCC patients. Moreover, miR-148a inhibit the malignant progression and increase the sensitivity of RCC cells to As2O3 by regulating WNT10a.