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Updated: Jul 30, 2025

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SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer

Ho Tsoi1, Nicholas Nok-Ching Fung1, Ellen P S Man1

  • 1Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Cancers
|May 16, 2023
PubMed

Insights

Tamoxifen resistance in breast cancer is linked to BQ323636.1 (BQ) expression. Lower SRSF5 levels increase BQ, causing resistance. Overexpressing SRSF5 or inhibiting SRPK1 can reverse this, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oestrogen receptor-positive (ER +ve) breast cancer often requires adjuvant endocrine therapy like tamoxifen (TAM).
  • Tamoxifen resistance develops in approximately half of patients, limiting treatment efficacy.
  • BQ323636.1 (BQ), an NCOR2 splice variant, is implicated in conferring tamoxifen resistance.

Purpose of the Study:

  • To investigate the role of SRSF5 in regulating BQ expression and tamoxifen resistance.
  • To explore the therapeutic potential of modulating SRSF5 activity or its upstream regulators.

Main Methods:

  • In vitro and in vivo studies involving knockdown and overexpression of SRSF5.
  • Analysis of NCOR2 alternative splicing and BQ mRNA production.
  • Clinical investigation using tissue microarrays to correlate SRSF5 and BQ expression with patient outcomes.
  • Inhibition of SRPK1 kinase activity using SRPKIN-1.

Main Results:

  • Knockdown of SRSF5 increased BQ expression and conferred tamoxifen resistance, while SRSF5 overexpression reversed resistance.
  • A significant inverse correlation was observed between SRSF5 and BQ expression in clinical samples.
  • Low SRSF5 expression was associated with tamoxifen resistance, recurrence, metastasis, and poorer prognosis.
  • Inhibition of SRPK1 reduced SRSF5 phosphorylation, decreased BQ production, and diminished tamoxifen resistance.

Conclusions:

  • SRSF5 is a critical regulator of BQ expression and plays a key role in tamoxifen resistance.
  • Targeting SRSF5 activity presents a promising therapeutic strategy for overcoming tamoxifen resistance in ER +ve breast cancer.
  • SRPK1 inhibition offers a potential pathway to modulate SRSF5 and combat tamoxifen resistance.
Keywords:
BQ323636.1SRPK1SRSF5breast cancernovel targettamoxifen resistance

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