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Updated: Jul 9, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Lnc-PTCHD4-AS inhibits gastric cancer through MSH2-MSH6 dimerization and ATM-p53-p21 activation
Jingyun Wang1,2, Yang Mi1,2,3, Xiangdong Sun1,2
1Henan Key Laboratory for Helicobacter pylori and Microbiota and GI Cancer, Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
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.
Insights
A novel long non-coding RNA, PTCHD4-AS, is downregulated in gastric cancer (GC). Upregulating PTCHD4-AS inhibits GC cell proliferation and enhances cisplatin sensitivity by activating the ATM-p53-p21 pathway.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) roles in gastric cancer (GC) remain underexplored.
- PTCHD4-AS is a conserved lncRNA identified as downregulated in GC.
Purpose of the Study:
- To investigate the function and mechanism of the novel lncRNA PTCHD4-AS in gastric cancer.
- To explore PTCHD4-AS's potential as a therapeutic target for GC.
Main Methods:
- Identification and characterization of PTCHD4-AS in GC cell lines and tissues.
- Analysis of PTCHD4-AS expression in response to DNA damage agents.
- Investigation of PTCHD4-AS's role in cell cycle, apoptosis, and drug sensitivity.
- Molecular mechanism studies involving protein-RNA interactions and pathway analysis.
Main Results:
- PTCHD4-AS is conserved, downregulated in GC, and transcriptionally induced by DNA damage.
- PTCHD4-AS upregulation causes G2/M cell cycle arrest and enhances cisplatin-induced apoptosis in GC cells.
- PTCHD4-AS directly binds to the MSH2-MSH6 dimer, promoting ATM-p53-p21 pathway activation.
Conclusions:
- PTCHD4-AS inhibits GC cell proliferation and increases sensitivity to cisplatin.
- The mechanism involves PTCHD4-AS binding to MSH2-MSH6 and activating the ATM-p53-p21 signaling pathway.
- PTCHD4-AS represents a potential therapeutic target for gastric cancer treatment.
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