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Long Non-Coding RNA GAS5 Promotes BAX Expression by Competing with microRNA-128-3p in Response to 5-Fluorouracil

Heejin Lee1,2, Hoin Kang1, Chongtae Kim1

  • 1Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

Biomedicines
|January 21, 2023
PubMed

Insights

Long non-coding RNA GAS5 is downregulated in chemo-resistant colon cancer. Overexpressing GAS5 enhances anti-cancer drug efficacy by promoting apoptosis via BAX regulation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Drug resistance is a significant challenge in cancer therapy.
  • Mechanisms underlying cancer drug resistance require further elucidation.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in various cellular processes, including cancer progression and drug response.

Purpose of the Study:

  • To investigate the role of lncRNA GAS5 in the development of chemoresistance in colon cancer.
  • To elucidate the molecular mechanism by which GAS5 influences sensitivity to 5-fluorouracil (5-FU).

Main Methods:

  • Analysis of GAS5 expression in 5-FU-resistant colon cancer cell lines.
  • Assessment of cell viability and apoptosis markers (BAX) following GAS5 manipulation.
  • MS2-trap assay combined with RT-qPCR to determine GAS5-mRNA interactions.
  • Investigation of the regulatory relationship between GAS5, BAX, and microRNA-128-3p.

Main Results:

  • GAS5 was significantly downregulated in 5-FU-resistant colon cancer cells.
  • GAS5 downregulation reduced cell viability and BAX protein levels.
  • GAS5 overexpression promoted 5-FU-induced cell death.
  • GAS5 directly binds to the 3'-UTR of BAX mRNA, enhancing its expression by inhibiting miR-128-3p.
  • Ectopic GAS5 expression resensitized resistant cells to anti-cancer drugs.

Conclusions:

  • GAS5 plays a crucial role in overcoming 5-FU resistance in colon cancer.
  • GAS5 promotes apoptosis and enhances chemo-sensitivity by modulating the miR-128-3p/BAX axis.
  • GAS5 represents a potential therapeutic target for improving the efficacy of chemotherapy in resistant cancers.
Keywords:
BAXGAS5competing endogenous RNAlong non-coding RNAmicroRNA

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