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The oncogenic RNA-binding protein SRSF1 regulates LIG1 in non-small cell lung cancer

Elena Martínez-Terroba1,2, Teresa Ezponda1,2, Cristina Bértolo1,3

  • 1Program in Solid Tumors, CIMA, Pamplona, Spain.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|September 6, 2018
PubMed

Insights

The oncoprotein SRSF1 regulates DNA repair gene LIG1, impacting non-small cell lung cancer (NSCLC) progression. LIG1 expression is linked to poor prognosis in NSCLC patients, highlighting its role in lung cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Metabolism

Background:

  • RNA metabolism and RNA-binding proteins are increasingly implicated in various diseases, including cancer.
  • Alterations in RNA-binding protein levels can affect cancer-related gene expression.

Purpose of the Study:

  • To investigate if SRSF1 regulates DNA repair genes, specifically DNA ligase 1 (LIG1).
  • To determine the role of SRSF1-mediated regulation of LIG1 in lung carcinogenesis.
  • To assess the prognostic value of LIG1 in non-small cell lung cancer (NSCLC).

Main Methods:

  • In silico analysis to correlate SRSF1 and DNA repair gene expression.
  • In vitro functional assays using SRSF1 or LIG1-downregulated NSCLC cell lines.
  • Immunohistochemistry to evaluate LIG1 prognostic value in 210 NSCLC patients.

Main Results:

  • A significant correlation was found between SRSF1 and the DNA repair gene LIG1 in NSCLC cell lines.
  • SRSF1 binds to LIG1 mRNA, increasing its stability and translation via an mTOR-dependent pathway.
  • LIG1 inhibition reduced NSCLC cell proliferation and increased apoptosis.
  • LIG1 expression was identified as an independent prognostic factor for NSCLC.

Conclusions:

  • The oncoprotein SRSF1 regulates LIG1 expression, influencing lung cancer cell proliferation and progression.
  • LIG1 plays a significant role in lung carcinogenesis.
  • Elevated LIG1 expression is associated with a poor prognosis in NSCLC patients.

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