Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway

Lei Liu1, Xinlu Pang1, Wenjin Shang1

  • 1a Department of kidney transplantation , the First Affiliated Hospital of Zhengzhou University , Zhengzhou , Henan Province , P. R. China.

Insights

A long noncoding RNA, GAS5, is downregulated in sorafenib-resistant renal cell carcinoma (RCC). Restoring GAS5 may overcome resistance, suggesting GAS5 as a potential therapeutic target and biomarker for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sorafenib improves survival in renal cell carcinoma (RCC) but resistance occurs.
  • Understanding sorafenib resistance mechanisms and identifying biomarkers are crucial for effective RCC treatment.

Purpose of the Study:

  • To investigate the role of long noncoding RNA GAS5 in sorafenib resistance in RCC.
  • To identify GAS5 as a potential biomarker and therapeutic target for sorafenib treatment in RCC.

Main Methods:

  • Quantitative analysis of GAS5 expression in sorafenib-responsive and nonresponsive RCC.
  • In vitro and in vivo experiments involving GAS5 overexpression and knockdown in RCC cells.
  • Investigation of the molecular mechanism involving GAS5, miR-21, and SOX5.

Main Results:

  • GAS5 was significantly downregulated in sorafenib-nonresponsive RCC.
  • GAS5 overexpression sensitized nonresponsive RCC cells to sorafenib.
  • GAS5 knockdown induced sorafenib resistance in responsive RCC cells.
  • GAS5 acts as a competing endogenous RNA, repressing miR-21 and subsequently SOX5.

Conclusions:

  • GAS5 downregulation is associated with poor response to sorafenib in RCC.
  • The GAS5/miR-21/SOX5 axis plays a critical role in regulating sorafenib resistance in RCC.
  • GAS5 represents a potential predictive biomarker and therapeutic target for sorafenib treatment in RCC.

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