Upregulation of METTL14 mediates the elevation of PERP mRNA N 6 adenosine methylation promoting the growth and metastasi
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RESEARCH
Open Access
Upregulation of METTL14 mediates the elevation of PERP mRNA N6 adenosine methylation promoting the growth and metastasis of pancreatic cancer Min Wang1†, Jun Liu2†, Yan Zhao3†, Ruizhi He1†, Xiaodong Xu4†, Xingjun Guo1, Xu Li1, Simiao Xu5, Ji Miao6, Jianpin Guo7,8, Hang Zhang1, Jun Gong1, Feng Zhu1, Rui Tian1, Chengjian Shi1, Feng Peng1, Yechen Feng1, Shuo Yu1, Yu Xie1, Jianxin Jiang9, Min Li10*, Wenyi Wei8*, Chuan He2* and Renyi Qin1*
Abstract Background: Pancreatic cancer is one of the most lethal human cancers. N6-methyladenosine (m6A), a common eukaryotic mRNA modification, plays critical roles in both physiological and pathological processes. However, its role in pancreatic cancer remains elusive. Methods: LC/MS was used to profile m6A levels in pancreatic cancer and normal tissues. Bioinformatics analysis, real-time PCR, immunohistochemistry, and western blotting were used to identify the role of m6A regulators in pancreatic cancer. The biological effects of methyltransferase-like 14 (METTL14), an mRNA methylase, were investigated using in vitro and in vivo models. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of METTL14. (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected]; [email protected] † Min Wang, Jun Liu, Yan Zhao, Ruizhi He and Xiaodong Xu contributed equally to this work. 10 Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA 8 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA 2 Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA 1 Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero
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