Long non-coding RNA STMN1P2 promotes breast cancer doxorubicin resistance by inhibiting pyroptosis through the

You-Ping Jin1, Bu-Jie Xu1, Xiu-Fen Zhang1

  • 1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

Acta Pharmacologica Sinica
|September 9, 2025
PubMed

Insights

This study reveals that the long non-coding RNA STMN1P2 promotes chemoresistance in breast cancer by inhibiting pyroptosis. Reducing STMN1P2 levels can re-sensitize cancer cells to doxorubicin, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemotherapeutic resistance, particularly to doxorubicin, is a major challenge in breast cancer treatment.
  • Pyroptosis inhibition is linked to chemoresistance, and long non-coding RNAs (lncRNAs) are implicated in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the role of the lncRNA STMN1P2 in doxorubicin resistance in breast cancer.
  • To explore the correlation between STMN1P2 and pyroptosis inhibition in breast cancer cells.

Main Methods:

  • Quantitative real-time PCR to measure STMN1P2 expression in resistant vs. sensitive tissues and cells.
  • Cell viability assays and pyroptosis marker analysis (NLRP3, ASC, caspase-1, GSDMD) after STMN1P2 knockdown or overexpression.
  • RNA immunoprecipitation and Western blotting to assess interactions between STMN1P2, hnRNPU, EZH2, TRAF6, MALT1, and caspase-1.
  • Xenograft mouse models to evaluate the in vivo effect of STMN1P2 knockdown on tumor growth suppression by doxorubicin.

Main Results:

  • STMN1P2 expression was significantly higher in doxorubicin-resistant breast cancer tissues and cells.
  • Knockdown of STMN1P2 decreased doxorubicin resistance and restored pyroptosis.
  • STMN1P2 positively regulated hnRNPU, which in turn recruited EZH2 to suppress pyroptosis pathways (TRAF6-MALT1-caspase-1).
  • Knockdown of STMN1P2 in vivo significantly enhanced doxorubicin's tumor growth suppression.

Conclusions:

  • STMN1P2 plays a critical role in promoting doxorubicin resistance in breast cancer by inhibiting pyroptosis through the hnRNPU/EZH2/TRAF6 pathway.
  • Targeting STMN1P2 presents a promising strategy for overcoming breast cancer chemoresistance.

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