MiR-663b promotes colorectal cancer progression by activating Ras/Raf signaling through downregulation of TNK1.

Abstract

MiR-663b has been demonstrated to be abnormally expressed in several cancer types and was involved in the progression of cancer. Although overexpression of miR-663b in colorectal cancer was observed, the role of miR-663b in colorectal cancer cells has not been identified yet. In this study, we analyzed expression of miR-663b in colorectal tumors and explored the molecular mechanism of miR-663b in colorectal cancer cells. MiR-663b was significantly overexpressed in colorectal tumors and cell lines. Downregulation of miR-663b inhibited cell proliferation and sphere forming ability in colorectal cancer cells. In addition, miR-663b downregulation inactivated Ras/Raf signaling activity and subsequently decreased YAP1 and CD44 expression in colorectal cancer cells. Using TargetScan software, TNK1, a negative regulator of Ras/Raf signaling, was predicted to be a target gene of miR-663b. Western blotting and RT-qPCR showed that TNK1 expression was negatively regulated by miR-663b. In addition, the direct binding of miR-663b to TNK1 mRNA was proved by dual luciferase reporter assay. Furthermore, downregulation of miR-663b inhibited colorectal cancer cell proliferation and stemness, which was reversed after siRNA-mediated silencing of TNK1. In conclusion, the current study revealed a pivotal role of miR-663b in the progression of colorectal cancer.