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Updated: Aug 23, 2025

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TCL1A acts as a tumour suppressor by modulating gastric cancer autophagy via miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop

Jialing Hao1, Haitao Mei2, Qingshan Luo1

  • 1Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, China.

Carcinogenesis
|November 1, 2022
PubMed

Insights

TCL1A acts as a tumor suppressor in gastric cancer by regulating the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop. This pathway influences gastric cancer cell autophagy, apoptosis, and progression, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Gastric cancer is a leading cause of cancer death globally and highly prevalent in China.
  • TCL1A (TCL1 family Akt coactivator A) influences the Akt/mTOR pathway and autophagy, but its role in gastric cancer remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of TCL1A action in gastric cancer.
  • To investigate the regulatory loop involving miR-181a-5p, TCL1A, Akt/mTOR, and c-MYC in gastric cancer.

Main Methods:

  • Analysis of TCL1A expression in gastric cancer tissues.
  • Investigation of the miR-181a-5p-TCL1A-Akt/mTOR-c-MYC feedback loop.
  • Flow cytometry for apoptosis assays and mRFP-eGFP-LC3 assays for autophagy.
  • In vivo experiments to assess TCL1A's effect on tumor proliferation.

Main Results:

  • TCL1A was found to be downregulated in gastric cancer tissues.
  • A feedback loop (miR-181a-5p-TCL1A-Akt/mTOR-c-MYC) was identified, regulating miR-181a-5p and c-MYC.
  • Both miR-181a-5p and TCL1A were shown to modulate autophagy and apoptosis in gastric cancer cells via this loop.
  • TCL1A demonstrated an inhibitory effect on gastric cancer proliferation in vivo.

Conclusions:

  • TCL1A exhibits tumor-suppressive effects in gastric cancer.
  • The miR-181a-5p-TCL1A-Akt/mTOR-c-MYC loop is crucial for regulating gastric cancer autophagy and progression.
  • This regulatory loop represents a potential therapeutic target for gastric cancer treatment.

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