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Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma

Z Xu1, F Yang2, D Wei3

  • 1Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Oncogene
|November 15, 2016
PubMed

Insights

A novel long non-coding RNA, lncRNA-SRLR, drives sorafenib resistance in renal cell carcinoma (RCC) by activating the IL-6/STAT3 pathway. Targeting lncRNA-SRLR may improve treatment response in RCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

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

Purpose of the Study:

  • To identify novel biomarkers and therapeutic targets for sorafenib resistance in RCC.
  • To elucidate the molecular mechanisms underlying sorafenib resistance in RCC.

Main Methods:

  • Identification and characterization of a long non-coding RNA (lncRNA-SRLR) in sorafenib-resistant RCC cells.
  • lncRNA-SRLR knockdown and overexpression experiments to assess its role in sorafenib sensitivity.
  • Mechanistic studies involving NF-κB, IL-6, and STAT3 pathways.
  • Clinical investigation correlating lncRNA-SRLR levels with patient response to sorafenib therapy.

Main Results:

  • lncRNA-SRLR is upregulated in intrinsically sorafenib-resistant RCC.
  • lncRNA-SRLR knockdown sensitizes resistant RCC cells to sorafenib; overexpression confers resistance.
  • lncRNA-SRLR promotes IL-6 transcription via NF-κB, activating STAT3 and causing sorafenib tolerance.
  • STAT3 inhibition and IL-6 receptor antagonism restore sorafenib sensitivity.
  • High lncRNA-SRLR levels correlate with poor sorafenib treatment response in RCC patients.

Conclusions:

  • lncRNA-SRLR is a key driver of sorafenib resistance in RCC.
  • lncRNA-SRLR serves as a predictive biomarker for sorafenib resistance.
  • Targeting lncRNA-SRLR presents a potential therapeutic strategy to overcome sorafenib resistance in RCC.

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