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Updated: Jun 10, 2025

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Aberrant FAM135B attenuates the efficacy of chemotherapy in colorectal cancer by modulating SRSF1-mediated

Wanmei Lin1,2, Lijun Xu2, Yaoying Li2

  • 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Oncogene
|October 13, 2024
PubMed

Insights

Sequence similarity 135 family member B (FAM135B) drives colorectal cancer (CRC) proliferation and oxaliplatin insensitivity by controlling DNA repair splicing. Targeting FAM135B may improve CRC treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oxaliplatin is a primary chemotherapy for colorectal cancer (CRC), but treatment resistance is a significant challenge.
  • Genomic instability in CRC correlates with treatment response, yet mechanisms of oxaliplatin insensitivity are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying oxaliplatin insensitivity in colorectal cancer.
  • To identify novel genetic factors and pathways involved in CRC chemoresistance.

Main Methods:

  • Utilized genetic mutation analysis in CRC to identify key genes.
  • Investigated the role of FAM135B in regulating alternative splicing and DNA repair pathways.
  • Examined the interaction between FAM135B, SRSF1, SRPK1, and DNA repair proteins.

Main Results:

  • FAM135B is frequently mutated in CRC and promotes CRC proliferation and oxaliplatin insensitivity.
  • FAM135B controls SRSF1-mediated alternative splicing, including exon IV inclusion of FAAP20.
  • This splicing event enhances the FA core complex, activating DNA repair pathways and conferring oxaliplatin resistance.

Conclusions:

  • The FAM135B-SRSF1 axis regulates DNA repair and contributes to chemotherapeutic insensitivity in CRC.
  • FAM135B is a potential therapeutic target for overcoming oxaliplatin resistance in colorectal cancer treatment.

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