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Dysregulation of alternative splicing contributes to multiple myeloma pathogenesis

Sha Song1, Weimin Zhang2, Qi Li2

  • 1Department of Cell Biology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China.

British Journal of Cancer
|January 2, 2023
PubMed
Abstract

Insights

Alternative splicing (AS) dysregulation drives multiple myeloma (MM) tumorigenesis. SRSF1 upregulation promotes MM and predicts poor prognosis, offering a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Dysregulation of alternative splicing (AS) is implicated in tumorigenesis.
  • Understanding AS in multiple myeloma (MM) can reveal new therapeutic and prognostic strategies.

Purpose of the Study:

  • To investigate the role of splicing factors (SFs) in multiple myeloma (MM) pathogenesis.
  • To identify potential therapeutic targets and prognostic biomarkers for MM.

Main Methods:

  • Utilized molecular, genetic, bioinformatic, and statistical approaches.
  • Analyzed myeloma cell lines, xenograft models, and patient samples.
  • Employed Gene Set Enrichment Analysis (GSEA) and RNA-Sequencing (RNA-Seq).

Main Results:

  • Alternative splicing pathway genes are significantly enriched in MM patients.
  • SRSF1 is upregulated in MM progression, correlating with poor prognosis and promoting tumorigenesis by altering AS events.
  • SRSF1 knockdown demonstrated anti-myeloma activity in vitro and in vivo; YY1 transcription factor drives SRSF1 upregulation.

Conclusions:

  • Alternative splicing plays a critical role in promoting MM tumorigenesis.
  • SRSF1 is a potential prognostic biomarker and therapeutic target for MM.

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