Downregulation of miR-19a exhibits inhibitory effects on metastatic renal cell carcinoma by targeting PIK3CA and inactivating Notch signaling in vitro

Abstract

Metastasis seriously affects the clinical outcome of renal cell carcinoma patients. Despite the approval of several targeted therapies that have led to an improvement in the progression-free survival rate for these patients, advanced and metastatic renal cell carcinoma remains difficult to treat. Recently, microRNAs have been found to play a critical role in the metastatic dissemination of renal cell carcinoma cells. In the present study, we found that miR-19a expression was significantly upregulated in metastatic clear cell renal carcinoma than that in adjacent and primary carcinoma tissues using qPCR and in situ hybridization experiments. In addition, the results were confirmed in renal carcinoma cell lines. miR-19a expression in the cell lines derived from a metastatic site was higher than that in cell lines derived from a primary site. By gain- and loss-of-function experiments, we found that miR-19a acted as an oncogenic miRNA regulating renal cancer cell proliferation, migration and invasion by directly targeting PIK3CA. Furthermore, we also explored the down-stream molecules of miR-19a/PIK3CA signaling. We found that Notch signaling was induced by upregulation of miR-19a, and inactivation of Notch signaling attenuated the cell proliferation, migration and invasion promoted by miR-19a. Thus, we provide evidence demonstrating that downregulation of miR-19a may be therapeutically beneficial for metastatic renal carcinoma.