基因敲除
癌症研究
小发夹RNA
上皮-间质转换
卵巢癌
卵巢癌
基因沉默
下调和上调
小RNA
医学
运动性
癌症
内科学
肿瘤科
生物
细胞生长
细胞培养
转移
细胞生物学
基因
遗传学
生物化学
作者
Wenfeng Hua,Yuan Zhao,Xiaojuan Jin,Danyang Yu,Jing He,Dan Xie,Peng Duan
标识
DOI:10.1016/j.ygyno.2018.09.015
摘要
Objective As the most prevalent internal modification in mammalian messenger RNA, N6‑methyladenosine (m6A) plays an important role in posttranscriptional gene regulation. METTL3 is a key component of the m6A methyltransferase complex and has recently been shown to play important roles in cancer development and progression. The current study was aimed to explore the function and underlying mechanism of METTL3 in ovarian cancer. Methods METTL3 expression was assessed by immunohistochemistry in 162 ovarian carcinoma patients. Stable cell lines with METTL3 gene overexpression or knockdown were established to investigate the function of METTL3 in ovarian cancer in vitro and in vivo. Results METTL3 was frequently upregulated in ovarian carcinoma and that a high level of METTL3 was significantly associated with tumor grade (P = 0.001), pT status (P = 0.002), pN/pM status (P < 0.001), FIGO stage (P < 0.001), and overall survival rate (P < 0.001). Stable overexpression of METTL3 in the OVCAR3 and COV504 cell lines significantly increased cellular proliferation, focus formation, motility, invasion, and tumor formation in nude mice. Silencing METTL3 expression in the SKOV3 and HO-8910 cell lines with short hairpin RNA effectively inhibited its oncogenic function. Further study found that METTL3 promoted epithelial-mesenchymal transition (EMT) by upregulating the receptor tyrosine kinase AXL. Conclusion Our findings suggest that METTL3 plays very important oncogenic roles in ovarian carcinoma development and/or aggressiveness by stimulating AXL translation and EMT and that METTL3 may serve as a novel prognostic and/or therapeutic target of interest in ovarian cancer.
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