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Updated: Sep 7, 2025

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SOCS5 contributes to temozolomide resistance in glioblastoma by regulating Bcl-2-mediated autophagy

Jie Yu1, Lin Han2, Feng Yang3

  • 1Department of Neurosurgery, Hunan Provincial People's Hospital, Changsha, Hunan, China.

Bioengineered
|June 22, 2022
PubMed

Insights

High SOCS5 expression correlates with poor glioblastoma prognosis and temozolomide resistance. SOCS5 promotes drug resistance by upregulating autophagy via Bcl-2, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Temozolomide (TMZ) is a primary treatment for glioblastoma (GBM), but drug resistance limits efficacy.
  • Autophagy's role in chemotherapy resistance and cancer survival is implicated but not fully understood.
  • The function of the suppressor of cytokine signaling (SOCS) family in GBM and its association with drug resistance is largely unknown.

Purpose of the Study:

  • To investigate the expression pattern and role of SOCS family members in GBM.
  • To elucidate the molecular mechanisms by which SOCS5 contributes to temozolomide resistance in GBM.
  • To determine if SOCS5 can serve as a prognostic marker or therapeutic target for drug-resistant GBM.

Main Methods:

  • Assessed SOCS5 expression levels in GBM patient samples and correlated them with prognosis and TMZ resistance.
  • Investigated the effect of TMZ treatment on SOCS5 expression and autophagy.
  • Utilized gene knockdown and overexpression techniques to study the role of SOCS5 and Bcl-2 in TMZ resistance and autophagy.
  • Analyzed the transcriptional regulation of Bcl-2 by SOCS5.

Main Results:

  • High SOCS5 expression was significantly associated with poor prognosis and resistance to TMZ in GBM.
  • TMZ treatment increased SOCS5 expression and induced autophagy, which was dependent on SOCS5.
  • SOCS5 enhances Bcl-2 transcription, leading to increased autophagy and TMZ chemoresistance.
  • Knockdown of SOCS5 reversed TMZ resistance by inhibiting Bcl-2-mediated autophagy, an effect that could be overcome by Bcl-2 upregulation.

Conclusions:

  • SOCS5 plays a critical role in mediating TMZ resistance in GBM through the upregulation of autophagy via Bcl-2.
  • SOCS5 represents a potential prognostic biomarker and a novel therapeutic target for overcoming chemoresistance in GBM patients.
Keywords:
Bcl-2GlioblastomaSOCS5autophagyresistancetemozolomide

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