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

Abstract

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 protooncogenic 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 CREB1 in RCC. CREB1 was overexpressed in the RCC tissues and cell lines. Downregulation of CREB1 inhibited RCC tumorigenesis by affecting cell proliferation, migration and apoptosis. Multiple computational algorithms predicted that the 3'untranslated region (3'UTR) of human CREB1 mRNA is a target for miR10b5p and miR3633p. Luciferase reporter assay, qPCR and western blot analysis confirmed that miR10b5p and miR3633p bind directly to the 3'UTR of CREB1 mRNA and inhibit mRNA and protein expression of CREB1. qPCR data also revealed a significantly lower expression of miR10b5p and miR3633p in RCC tissues. Introduction of miR10b5p and miR3633p mimics led to suppressed expression of CREB1 and inhibited cell proliferation, migration and apoptosis reduction. Taken together, we propose that CREB1 is an oncogene in RCC and that upregulation of CREB1 by loss of tumor suppressive miR10b5p and miR3633p plays an important role in the tumorigenesis of RCC.