N6-methyladenosine (m6A) RNA methylation, one of the common RNA modifications, has been determined to execute crucial functions on tumorigenesis and cancer development. The m6A “writers” including Methyltransferase like 3 (METTL3), METTL14 and Wilms tumor 1-associated protein (WTAP) contribute to the m6A modification process initiation. However, the coordination of m6A methyltransferase complex is not fully understood in endometrioid epithelial ovarian cancer (EEOC). In this study, mRNA and protein levels of METTL3, METTL14 and WTAP were detected in 33 EEOC cases using qPCR, immunohistochemistry and western blot. The overall m6A methylation was detected by dot plot. The METTL3 expression and overall m6A level were elevated in EEOC tissues, while the expressions of METTL14 and WTAP have no significant difference in EEOC compared to the adjacent tissues. The expression of METTL3 was an independent factor to correlate with poor malignancy and survival of EEOC patients. Moreover, METTL3 knockdown in TOV-112D and CRL-11731D cells weakened the capability of cell proliferation and migration, and promoted the cell apoptosis compared to negative control and cells with WTAP or METTL14 knockdown using CCK-8 assay, transwell assay, wound healing assay and TUNEL assay. Furthermore, METTL3 knockdown also reduced m6A enrichment of the genes associated with ovarian cancer including EIF3C, AXL, CSF-1, FZD10 in TOV-112D and CRL-11731D cells by RIP-qPCR assay. Taken together, the high expressed METTL3 indicated poor malignancy and survival of EEOC via modulating the aberrant m6A RNA methylation. METTL3-mediated m6A modification, independent of WTAP and METTL14, was considered as a novel mechanism underlying m6A modulation and a potential therapeutic target of EEOC. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.