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RNA-binding motif protein 35A is a novel tumor suppressor for colorectal cancer

Olga V Leontieva1, Yuri Ionov

  • 1Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

Cell Cycle (Georgetown, Tex.)
|January 30, 2009
PubMed

Insights

RNA binding motif protein 35A (RBM35A) acts as a tumor suppressor in colon cancer. Its expression inhibits cancer cell growth and affects gene translation through messenger RNA 5' untranslated regions.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Gene mutations in tumors often indicate tumor suppressor roles.
  • RNA binding motif protein 35A (RBM35A) is frequently mutated in colon tumors with microsatellite instability.

Purpose of the Study:

  • To investigate the tumor suppressor function of RBM35A in colon cancer.
  • To elucidate the mechanism by which RBM35A regulates gene expression.

Main Methods:

  • Ectopic expression of RBM35A in RBM35A-null colon carcinoma cells.
  • Microarray analysis to assess changes in polysome-associated mRNA.
  • In vitro translation assays using luciferase reporters with varying 5' untranslated regions (UTRs).
  • Site-directed mutagenesis of FOS 5' UTR to alter secondary structure stability.
  • Immunoblotting to analyze protein levels of cancer-related genes.

Main Results:

  • RBM35A expression inhibited anchorage-independent growth, suppressed tumorigenic potential, and enhanced cancer cell adhesion.
  • RBM35A expression led to decreased polysome-associated mRNA for a subset of genes.
  • RBM35A differentially affected translation efficiency mediated by various 5' UTRs, correlated with their secondary structure stability (Gibbs energy, DeltaG).
  • Mutating the FOS 5' UTR to increase hairpin stability enhanced RBM35A's inhibitory effect on translation.
  • Ectopic RBM35A expression altered protein levels of several cancer-related genes.

Conclusions:

  • RBM35A functions as a tumor suppressor in colon cancer cells.
  • RBM35A is involved in posttranscriptional gene regulation by modulating protein translation.
  • The differential effect of RBM35A on translation is mediated by the secondary structure of mRNA 5' UTRs.

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