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

Abstract

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.

Inhibition of zinc finger protein 367 exerts a tumor suppressive role in colorectal cancer by affecting the activation of oncogenic YAP1 signaling

“…YAP1 signaling plays a key role in the progression of colorectal cancer 28,33–36 . Nuclear levels of YAP1 are frequently up‐regulated in colorectal cancer, and the expression of YAP1 target genes, such as CTGF and CRY61, is also increased 23,37,38 .…”

“…The luciferase reporter assay of YAP1 was performed in accordance with a previously described method 28 …”

RETRACTED ARTICLE: MCM3AP-AS1/miR-876-5p/WNT5A axis regulates the proliferation of prostate cancer cells

“…MiR-487a-3p serves as a tumor suppressor in prostate cancer by targeting CCND1 (cyclin D1, CCND1) [ 33 ]. MiR-876-5p has been validate as a tumor suppressor in multiple tumors including breast cancer, gastric cancer, colorectal cancer, head and neck squamous cell carcinoma, liver cancer and so on [ 16 , 17 , 34 – 36 ], and its downstream targets includes TFAP2A, MITF, RASAL2, vimentin, DNMT3A and so on [ 16 , 17 , 34 – 36 ]. In this study, for the first time, we found that miR-876-5p was remarkably down-regulated in PCa tissues and cells, and could inhibit the proliferation of PCa cells.…”

Inhibition of Ras protein activator like 2 produces antitumor effects in gastric cancer via the suppression of YAP1 activation

“…It has been documented that RASAL2 exerts tumor‐promoting behavior by enhancing the activation of the oncogenic protein YAP1 14,29 . Inhibition of RASAL2 up‐regulated the phosphorylation of YAP1, and increased translocation of YAP1 from the nucleus to cytoplasm, leading YAP1 inactivation in colorectal cancer cells 14 .…”