Research Paper Volume 15, Issue 22 pp 13558—13578
Lnc-PTCHD4-AS inhibits gastric cancer through MSH2-MSH6 dimerization and ATM-p53-p21 activation
- 1 Henan Key Laboratory for Helicobacter pylori and Microbiota and GI Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
- 2 Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China
- 3 Department of Gastroenterology, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
Received: August 25, 2023 Accepted: November 6, 2023 Published: November 27, 2023
https://doi.org/10.18632/aging.205329How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Conserved long non-coding RNAs (lncRNAs) have not thoroughly been studied in many cancers, including gastric cancer (GC). We have identified a novel lncRNA PTCHD4-AS which was highly conserved between humans and mice and naturally downregulated in GC cell lines and tissues. Notably, PTCHD4-AS was found to be transcriptionally induced by DNA damage agents and its upregulation led to cell cycle arrest at the G2/M phase, in parallel, it facilitated the cell apoptosis induced by cisplatin (CDDP) in GC. Mechanistically, PTCHD4-AS directly bound to the DNA mismatch repair protein MSH2-MSH6 dimer, and facilitated the binding of dimer to ATM, thereby promoting the expression of phosphorylated ATM, p53 and p21. Here we conclude that the upregulation of PTCHD4-AS inhibits proliferation and increases CDDP sensitivity of GC cells via binding with MSH2-MSH6 dimer, activating the ATM-p53-p21 pathway.