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Research Paper|Volume 12, Issue 21|pp 21638—21659

Analysis of METTL3 and METTL14 in hepatocellular carcinoma

Xiangxiang Liu1, Jian Qin2, Tianyi Gao2, Chenmeng Li1, Xiaoxiang Chen2, Kaixuan Zeng1, Mu Xu2, Bangshun He2, Bei Pan2, Xueni Xu1, Yuqin Pan2, Huiling Sun2, Tao Xu2, Shukui Wang1,3
  • 1School of Medicine, Southeast University, Nanjing 210096, Jiangsu, China
  • 2General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China
  • 3Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211100, Jiangsu, China
Received: April 10, 2020Accepted: August 1, 2020Published: November 6, 2020
https://doi.org/10.18632/aging.103959

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

N6-methyladenosine (m6A) RNA methylation is the most prevalent modification of messenger RNAs (mRNAs) and catalyzed by a multicomponent methyltransferase complex (MTC), among which methyltransferase-like 3 (METTL3) and METTL14 are two core molecules. However, METTL3 and METTL14 play opposite regulatory roles in hepatocellular carcinoma (HCC). Based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, we conducted a multi-omics analysis of METTL3 and METTL14 in HCC, including RNA-sequencing, m6ARIP-sequencing, and ribosome-sequencing profiles. We found that the expression and prognostic value of METTL3 and METTL14 are opposite in HCC. Besides, after METTL3 and METTL14 knockdown, most of the dysregulated mRNAs, signaling pathways and biological processes are distinct in HCC, which partly explains the contrary regulatory role of METTL3 and METTL14. Intriguingly, these mRNAs whose stability or translation efficiency are influenced by METTL3 or METTL14 in an m6A dependent manner, jointly regulate multiple signaling pathways and biological processes, which supports the cooperative role of METTL3 and METTL14 in catalyzing m6A modification. In conclusion, our study further clarified the contradictory role of METTL3 and METTL14 in HCC.