Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

Highlights: ► This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. ► Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. ► c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. ► The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17–92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.