m6A modification-mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability

Deliang Fang1,2, Xinde Ou1,2, Kaiyu Sun1

  • 1Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Cancer Science
|September 17, 2022
PubMed

Insights

The long noncoding RNA TP53TG1 acts as a tumor suppressor in gastric cancer (GC). Its downregulation promotes GC progression, offering a potential therapeutic target for this disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are implicated in cancer, but their specific roles in tumor progression are often unknown.
  • Gastric cancer (GC) remains a significant health concern with a need for novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of the lncRNA TP53TG1 in gastric cancer.
  • To elucidate the molecular mechanisms underlying TP53TG1's function in GC progression.

Main Methods:

  • Quantitative analysis of TP53TG1 expression in GC tissues and cell lines.
  • Functional assays to assess the impact of TP53TG1 on GC cell proliferation, migration, invasion, cell cycle, and apoptosis.
  • Investigation of the regulatory role of ALKBH5 on TP53TG1 stability and expression.
  • Analysis of TP53TG1 interaction with CIP2A and its effect on the PI3K/AKT pathway.

Main Results:

  • TP53TG1 expression was significantly downregulated in GC tissues and correlated with poor patient survival.
  • Overexpression of TP53TG1 suppressed GC cell proliferation, metastasis, and cell cycle progression, while promoting apoptosis.
  • ALKBH5 was found to destabilize TP53TG1, leading to its reduced expression.
  • TP53TG1 induced the degradation of CIP2A, consequently inhibiting the PI3K/AKT signaling pathway.

Conclusions:

  • TP53TG1 functions as a tumor suppressor in gastric cancer.
  • The ALKBH5-TP53TG1-CIP2A axis regulates GC progression via the PI3K/AKT pathway.
  • TP53TG1 represents a promising therapeutic target for gastric cancer treatment.

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