TGF-[beta]1 affects the renal cancer miRNome and regulates tumor cells proliferation

TGF-[beta]1 is a pleiotropic cytokine that can either promote or inhibit cancer development and progression. It was previously found that TGF-[beta]1 can regulate the expression of several microRNAs (miR or miRNA) involved in the progression of renal cell carcinoma (Rcc). Therefore, the present study aimed to analyze the effects of TGF-[beta]1 on the global Rcc miRNome. It was found that TGF-[beta]1 can regulate a complex network consisting of miRNAs and mRNAs involved in Rcc transformation. In particular, TGF-[beta]1 was revealed to regulate the proliferation of Rcc cells while concomitantly modifying the expression of oncogenic regulators, including avian erythroblastosis virus E26 (V-Ets) oncogene homolog-1 (ETS1). In addition, TGF-[beta]1 was demonstrated to regulate the expression of a number of miRNAs including miR-30c-5p, miR-155-5p, miR-181a-5p and miR-181b-5p. By contrast, TGF-[beta]1 reciprocally modified the expression of genes encoding TGF-[beta]1 receptors and SMAds, indicating a novel regulatory feedback mechanism mediated through the miRNAs. These data suggested that ETS1 served different roles in different subtypes of RCC tumors, specifically by functioning as an oncogene in clear cell Rcc while as a tumor suppressor in papillary Rcc.