国内团队:METTL14对miR-375的m6A修饰可抑制结直肠癌
创作:szx 审核:szx 2019年12月16日
  • 对比112份结直肠癌样本及癌旁正常组织,并对比6种结直肠癌细胞系及正常结肠上皮细胞,发现结直肠癌中的甲基转移酶样蛋白14(METTL14)表达显著下调;
  • METTL14的表达降低与结直肠癌患者更短的总生存期显著相关;
  • 敲低METTL14可显著降低总RNA中的m6A水平,并促进结直肠癌细胞的生长及转移;
  • 过表达METTL14可显著增加总RNA中的m6A水平,并抑制结直肠癌细胞的生长及转移;
  • miR-375(在多种癌症中起到肿瘤抑制功能)是METTL14的靶点。
主编推荐语
szx
N6-甲基腺苷(m6A)修饰常见于RNA分子,可对RNA起到保护性作用,但其在结直肠癌中的作用尚未明确。来自南京大学医学院附属金陵医院与南京医科大学附属南京第一医院的团队在Molecular Therapy上发表的一项最新研究,发现在结直肠癌样本及细胞系中,甲基转移酶样蛋白14(METTL14)的表达降低,且与结直肠癌患者较短的总生存期相关。机制上,METTL14可促进miR-375的m6A修饰,而后者对多种肿瘤有抑制作用。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Molecular Therapy [IF:8.402]

METTL14 suppresses colorectal cancer progression via regulating N6-methyladenosine-dependent primary miR-375 processing

METTL14通过调节N6-甲基腺苷依赖性miR-375加工以抑制结直肠癌进展

10.1016/j.ymthe.2019.11.016

2019-11-20, Article

Abstract & Authors:展开

Abstract:收起
Epigenetic alterations contributed to human carcinogenesis immensely. N6-methyladenosine (m6A) is one of the most preventive and abundant modifications on RNA molecules present in eukaryotes. However, the biological function of m6A methylation in colorectal cancer(CRC) remains largely unclear. Here, we found that METTL14 was downregulated in CRC tissues and cell lines and closely correlated with overall survival (OS). METTL14 knockdown significantly reduced m6A levels in total RNAs and promoted CRC cell growth and metastasis, whereas METTL14 overexpression markedly increased m6A levels in total RNA and inhibited CRC cell growth and metastasis. Furthermore, we demonstrated that miR-375 was a downstream target of METTL14. We also verified that METTL14 suppressed CRC cell growth via the miR-375/YAP1 pathway as well as inhibited CRC cell migration and invasion through the miR-375/SP1 pathway. Taken together, our studies showed an important role for METTL14 in CRC progression and provided novel insight into m6A modification in CRC progression.

First Authors:
Xiaoxiang Chen,Mu Xu

Correspondence Authors:
Xinyi Xia,Shukui Wang

All Authors:
Xiaoxiang Chen,Mu Xu,Xueni Xu,Kaixuan Zeng,Xiangxiang Liu,Li Sun,Bei Pan,Bangshun He,Yuqin Pan,Huiling Sun,Xinyi Xia,Shukui Wang

评论