Oncogenic cAMP responsive element binding protein 1 is overexpressed upon loss of tumor suppressive miR-10b-5p and miR-363-3p in renal cancer

Renal cell carcinoma (RCC) is the most common kidney cancer in adults and has a poor prognosis. cAMP responsive element binding protein 1(CREB1) is a proto-oncogenic transcription factor involved in malignancies of various organs. However, its functional role(s) have not yet been elucidated in RCC. We investigated the expression pattern, function and regulation of CREBI in RCC. CREBI was overexpressed in the RCC tissues and cell lines. Downregulation of CREBI inhibited RCC tumorigenesis by affecting cell proliferation, migration and apoptosis. Multiple computational algorithms predicted that the 3'-untranslated region (3'-UTR) of human CREBI mRNA is a target for miR-10b-5p and miR-363-3p. Luciferase reporter assay, qPCR and western blot analysis confirmed that miR-10b-5p and miR-363-3p bind directly to the 3'-UTR of CREBI mRNA and inhibit mRNA and protein expression of CREBI. qPCR data also revealed a significantly lower expression of miR-10b-5p and miR-363-3p in RCC tissues. Introduction of miR-10b-5p and miR-363-3p mimics led to suppressed expression of CREB1 and inhibited cell proliferation, migration and apoptosis reduction. Taken together, we propose that CREBI is an oncogene in RCC and that upregulation of CREBI by loss of tumor suppressive miR-10b-5p and miR-363-3p plays an important role in the tumorigenesis of RCC.