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Overexpression of Growth-Arrest-Specific Transcript 5 Improved Cisplatin Sensitivity in Hepatocellular Carcinoma

Panxiong Zhao1, Xi Cui2, Liyan Zhao3

  • 1Department of Nuclear Medicine, The First Affiliated Hospital of Henan University, Kaifeng, China.

DNA and Cell Biology
|March 28, 2020
PubMed

Insights

Long noncoding RNA GAS5 is downregulated in liver cancer, contributing to cisplatin resistance. Overexpressing GAS5 can re-sensitize liver cancer cells to cisplatin by targeting miR-222, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and treatment.
  • Growth-arrest-specific transcript 5 (GAS5) is implicated in chemoresistance across various cancers, but its specific function in hepatocellular carcinoma (HCC) remains unclear.

Purpose of the Study:

  • To investigate the role and molecular mechanism of GAS5 in cisplatin (CDDP) resistance in HCC.
  • To determine if GAS5 can overcome CDDP resistance in HCC cells.

Main Methods:

  • Quantitative real-time PCR to assess GAS5 expression in HCC tissues and cell lines.
  • Cell viability assays to evaluate the effect of GAS5 overexpression on CDDP sensitivity.
  • MiRNA sequencing and bioinformatics analysis to identify downstream targets of GAS5.
  • Luciferase reporter assays to confirm the interaction between GAS5 and miR-222.

Main Results:

  • GAS5 expression was significantly downregulated in HCC tissues and cells, particularly in CDDP-resistant ones.
  • Low GAS5 expression correlated with poorer patient survival.
  • Overexpression of GAS5 sensitized CDDP-resistant HCC cell lines (HepG2/CDDP, Huh7/CDDP) to CDDP treatment.
  • GAS5 was found to function as a sponge for miR-222, thereby enhancing CDDP sensitivity.

Conclusions:

  • GAS5 plays a critical role in overcoming CDDP resistance in HCC.
  • GAS5 sensitizes HCC cells to CDDP by sponging miR-222.
  • GAS5 represents a potential therapeutic target for enhancing chemoresistance in HCC.
Keywords:
cisplatingrowth-arrest-specific transcript 5hepatocellular carcinomamiR-222

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