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SRSF3-mediated regulation of N6-methyladenosine modification-related lncRNA ANRIL splicing promotes resistance of pancreatic cancer to gemcitabine.

Abstract
Serine/arginine-rich splicing factor 3 (SRSF3) regulates mRNA alternative splicing of more than 90% of protein-coding genes, providing an essential source for biological versatility. This study finds that SRSF3 expression is associated with drug resistance and poor prognosis in pancreatic cancer. We also find that SRSF3 regulates ANRIL splicing and m6A modification of ANRIL in pancreatic cancer cells. More importantly, we demonstrate that m6A methylation on lncRNA ANRIL is essential for the splicing. Moreover, our results show that SRSF3 promotes gemcitabine resistance by regulating ANRIL's splicing and ANRIL-208 (one of the ANRIL spliceosomes) can enhance DNA homologous recombination repair (HR) capacity by forming a complex with Ring1b and EZH2. In conclusion, this study establishes a link between SRSF3, m6A modification, lncRNA splicing, and DNA HR in pancreatic cancer and demonstrates that abnormal alternative splicing and m6A modification are closely related to chemotherapy resistance in pancreatic cancer.
AuthorsZu-Wei Wang, Jing-Jing Pan, Jian-Fei Hu, Jia-Qiang Zhang, Long Huang, Yi Huang, Cheng-Yu Liao, Can Yang, Zhi-Wen Chen, Yao-Dong Wang, Bai-Yong Shen, Yi-Feng Tian, Shi Chen
JournalCell reports (Cell Rep) Vol. 39 Issue 6 Pg. 110813 (05 10 2022) ISSN: 2211-1247 [Electronic] United States
PMID35545048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • RNA, Long Noncoding
  • SRSF3 protein, human
  • Deoxycytidine
  • Serine-Arginine Splicing Factors
  • DNA
  • N-methyladenosine
  • Adenosine
  • Gemcitabine
Topics
  • Adenosine (analogs & derivatives, metabolism)
  • Alternative Splicing (genetics)
  • DNA (metabolism)
  • Deoxycytidine (analogs & derivatives)
  • Humans
  • Pancreatic Neoplasms (drug therapy, genetics)
  • RNA, Long Noncoding (genetics, metabolism)
  • Serine-Arginine Splicing Factors (genetics, metabolism)
  • Gemcitabine
  • Pancreatic Neoplasms

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