Small protein ERSP encoded by LINC02870 promotes triple negative breast cancer progression via IRE1α/XBP1s activation

Xiaolu Wang1,2, Qianqian Wang1, Hong Wang1

  • 1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.

PubMed

Insights

Researchers discovered a new protein, ERSP, encoded by LINC01870, that drives triple-negative breast cancer (TNBC) progression by activating ER stress. Targeting ERSP may offer new therapeutic strategies for TNBC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) lacks targeted therapies, relying primarily on chemotherapy.
  • Long noncoding RNAs (lncRNAs) have emerging roles beyond non-coding functions, including encoding small proteins.
  • The role of lncRNA-encoded proteins in cancer progression is largely unexplored.

Purpose of the Study:

  • To identify and characterize novel lncRNA-encoded proteins involved in TNBC.
  • To investigate the function of a newly identified protein, ERSP, in TNBC pathogenesis.
  • To explore ERSP as a potential therapeutic target for TNBC.

Main Methods:

  • Identification and characterization of a novel small protein (ERSP) encoded by LINC01870.
  • Analysis of ERSP expression in TNBC tissues and correlation with patient prognosis.
  • In vitro and in vivo studies to assess the impact of ERSP loss on TNBC growth and metastasis.
  • Investigation of ERSP's mechanism of action involving the endoplasmic reticulum (ER) stress pathway, specifically the IRE1α/XBP1s branch.

Main Results:

  • A novel small protein, ERSP, encoded by LINC01870, was identified and localized to the ER.
  • ERSP expression was significantly elevated in TNBC tissues and correlated with poor patient prognosis.
  • Loss of ERSP function suppressed TNBC cell growth and metastasis in vitro and in vivo.
  • ERSP was found to activate the IRE1α/XBP1s pathway, enhancing the unfolded protein response (UPR) and promoting ER stress-related gene expression.

Conclusions:

  • The lncRNA-encoded protein ERSP plays a significant pro-oncogenic role in TNBC by modulating ER stress.
  • ERSP's activation of the IRE1α/XBP1s pathway is crucial for its oncogenic functions.
  • ERSP represents a promising novel therapeutic target for triple-negative breast cancer.

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