MicroRNA-17 promotes cell proliferation and migration in human colorectal cancer by downregulating SIK1

Cancer Manag Res. 2019 Apr 24:11:3521-3534. doi: 10.2147/CMAR.S191087. eCollection 2019.

Abstract

Purpose: There is mounting evidence to indicate that microRNA-17 (miR-17) is expressed and functionally involved in human cancers. However, the molecular mechanism underlying the role of miR-17 in colorectal cancer (CRC) remains largely unclear. This study aims to reveal the biological function of miR-17 in colorectal cancer. Materials and methods: The expression of miR-17 in CRC cells and tissues was examined using qRT-PCR. Cell proliferation and migration assays were performed after transfection with an miR-17 mimic and inhibitors. The potential gene targets of miR-17 were predicted by bioinformatics analysis and further validated by PCR, Western blot and dual luciferase reporter assays. Results: The expression of miR-17 was significantly upregulated in CRC cell lines and tissues and may imply poor prognosis. miR-17 upregulation promoted cell invasion and migration in CRC cell lines in vitro, while downregulation of miR-17 inhibited tumor progression. SIK1 was identified as a potential direct target of miR-17 by dual luciferase reporter assay, and its downregulation in CRC may suggest poor prognosis. Conclusions: Our study indicated that upregulated miR-17 may promote the progression of CRC and may exert its function as a tumor suppressor miRNA by targeting SIK1.

Keywords: SIK1; colorectal cancer; prognosis; tumor biomarker.