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.

Aging
|November 28, 2023
PubMed

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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