MicroRNA‐876‐5p represses the cell proliferation and invasion of colorectal cancer through suppressing YAP signalling via targeting RASAL2.

Ren, Li; Zhang, Zhiyong; Feng, Yun; Luo, Miaosha; Hao, Zhiming

Aberrant expression of microRNA‐876‐5p (miR‐876‐5p) is implicated in the progression of multiple human cancers. However, the potential role of miR‐876‐5p in colorectal cancer remains poorly understood. The purpose of the current study was to investigate the potential role of miR‐876‐5p in colorectal cancer. miR‐876‐5p expression was significantly downregulated in colorectal cancer tissues and cell lines compared with normal controls. Gain‐of‐function assays revealed that miR‐876‐5p overexpression effectively repressed the malignant behaviours of colorectal cancer cells, including cell proliferation, colony formation, and invasion. Bioinformatics analysis predicted that RAS protein activator like 2 (RASAL2), a potential oncogene for colorectal cancer, is a putative miR‐876‐5p target gene. A luciferase reporter assay confirmed that miR‐876‐5p directly binds to the 3′‐untranslated region (UTR) of RASAL2. Furthermore, both RASAL2 messenger RNA (mRNA) and protein expression were negatively modulated by miR‐876‐5p in colorectal cancer cells. Notably, there was an inverse correlation between miR‐876‐5p and RASAL2 expression in colorectal cancer tissue specimens. Moreover, miR‐876‐5p was involved in regulating the activation of Yes‐associated protein (YAP) signalling through inhibiting RASAL2. However, the miR‐876‐5p‐mediated antitumour effect on colorectal cancer cells was partially reversed by restoring RASAL2 expression. Notably, miR‐876‐5p upregulation impeded the tumour growth of colorectal cancer cells in vivo in nude mice. Overall, these results demonstrated that miR‐876‐5p exerts an antitumour function in colorectal cancer by targeting RASAL2 to suppress YAP signalling activation. These findings highlight the importance of the miR‐876‐5p/RASAL2/YAP axis in colorectal cancer progression and suggest that miR‐876‐5p is a potential therapeutic target for treating colorectal cancer.

RAS oncogenes; COLORECTAL cancer; CELL proliferation; RAS proteins; CANCER cell growth; MESSENGER RNA

Clinical & Experimental Pharmacology & Physiology, 2020, Vol 47, Issue 5, p867

0305-1870

Academic Journal

10.1111/1440-1681.13264