The m6A modification of LncRNA LINC00200 regulated by WTAP accelerates glioma tumorigenesis by regulating Wnt/β-catenin pathway.

BACKGROUND: Several studies have delineated that dysregulated N6-methyladenosine (m6A) regulators participate in glioma progression. The objective of this study is to investigate the mechanism of Wilms' tumor 1-associating protein (WTAP)-mediated m6A modification of long noncoding RNA (lncRNA) LINC00200 in glioma. METHODS: The LINC00200 expression in glioma was analyzed by qRT-PCR. The expressions of WTAP and Wnt/β-catenin pathway associated proteins were determined via qRT-PCR or western blotting. The levels of WTAP-mediated m6A modification of LINC00200 was ascertained by MeRIP-qPCR. Functionally, the effects of LINC00200 knockdown and the interaction of WTAP with LINC00200 on the glioma cell characteristics were examined by CCK8, colony formation, and transwell migration/invasion assays. In vivo experiments were performed to verify the effect of LINC00200 on tumor growth. RESULTS: LINC00200 was overexpressed in glioma, and high LINC00200 level was related to higher-grade tumor. Moreover, its knockdown inhibited the malignant properties and expression of molecules related to Wnt/β-catenin pathway in glioma cell lines. In vivo, LINC00200 knockdown attenuated tumor growth. WTAP was also overexpressed in glioma tissues and demonstrated a positive association with LINC00200 expression. Furthermore, the relative enrichment of LINC00200 m6A was enhanced/reduced in a WTAP-dependent manner. Meanwhile, silencing LINC00200 partially reversed the malignant effects of WTAP overexpression in glioma. CONCLUSION: These results demonstrate that WTAP-mediated m6A modification of LINC00200 promotes glioma progression by modulating Wnt/β-catenin pathway.