METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP.

N6-methyladenosine (m6A) RNA methylation, one of the common RNA modifications, has been determined to execute crucial functions in 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 quantitative polymerase chain reaction (qPCR), immunohistochemistry, and western blot analysis. 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 that correlated 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 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.

Ma Z ，Li Q ，Liu P ，Dong W ，Zuo Y ... -  《-》

WTAP facilitates progression of hepatocellular carcinoma via m6A-HuR-dependent epigenetic silencing of ETS1.

Chen Y ，Peng C ，Chen J ，Chen D ，Yang B ，He B ，Hu W ，Zhang Y ，Liu H ，Dai L ，Xie H ，Zhou L ，Wu J ，Zheng S ... -  《Molecular Cancer》

Changes of N6-methyladenosine modulators promote breast cancer progression.

Wu L ，Wu D ，Ning J ，Liu W ，Zhang D ... -  《BMC CANCER》

Dysregulated N6-methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer.

Accumulating evidence implies that N6-methyladenosine (m6A) methylation participated in the tumorigenesis of gastric cancer (GC). Here we synthetically analyzing the prognostic value and expression profile of seven m6A methylation-relevant genes through silico analysis of sequencing data downloaded from The Cancer Genome Atlas, Kaplan-Meier plotter, and Gene Expression Omnibus database. We explored the methyltransferase-like 3 (METTL3) expression in GC cell line and tumor tissues by reverse transcription quantitative polymerase chain reaction and western blot analysis. The m6A methylation status of total RNA was measured by m6A RNA methylation quantification kit. Small interfering RNA was used to establish METTL3 knockdown cell lines. We also measure the proliferation and migration capability GC cell. Furthermore, we detect the epithelial cell mesenchymal transition marker and m6A methylation level after METTL3 knock down. Our result revealed that METTL3 was significantly increased in GC tissues compared with control in big crowd data sets. Survival analysis showed that METTL3 serve as a poor prognostic factor for GC patients. The expression level of METTL3 gradually increased with the progress of tumor stage and grade. GFI1 is an important transcription factor associated with METTL3. We verified the up-trend of METTL3 in messenger RNA and protein expression and observed a significant increase in the m6A methylation status of total RNA in the GC cells and tissues. METTL3 knockdown inhibited total RNA m6A methylation level, as well as cell proliferation and migration capacity. Moreover, METTL3 knockdown decreased α-smooth muscle actin. Taken together, our finding revealed that m6A methylation writer METTL3 serve as an oncogene in tumorigenesis of GC.

Liu T ，Yang S ，Sui J ，Xu SY ，Cheng YP ，Shen B ，Zhang Y ，Zhang XM ，Yin LH ，Pu YP ，Liang GY ... -  《-》

Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase.

Ping XL ，Sun BF ，Wang L ，Xiao W ，Yang X ，Wang WJ ，Adhikari S ，Shi Y ，Lv Y ，Chen YS ，Zhao X ，Li A ，Yang Y ，Dahal U ，Lou XM ，Liu X ，Huang J ，Yuan WP ，Zhu XF ，Cheng T ，Zhao YL ，Wang X ，Rendtlew Danielsen JM ，Liu F ，Yang YG ... -  《-》