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CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer

Xiaolin Wang1,2,3,4, Jingxin Li2, Xing Bian1,2,3,4

  • 1High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Proceedings of the National Academy of Sciences of the United States of America
|August 13, 2021
PubMed

Insights

Circular RNAs (circRNAs) regulate human cancers. This study identifies circURI1 as a gastric cancer (GC) regulator that suppresses metastasis by modulating alternative splicing through hnRNPM interaction.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized as crucial regulators in human cancers.
  • The specific roles and mechanisms of circRNAs in gastric cancer (GC) are not fully understood.

Purpose of the Study:

  • To identify and characterize novel circRNAs involved in gastric cancer progression.
  • To elucidate the molecular mechanisms by which identified circRNAs regulate GC cell migration, invasion, and metastasis.

Main Methods:

  • CircRNA profiling of gastric cancer (GC) and adjacent non-tumor tissues.
  • In vitro assays to assess cell migration and invasion.
  • In vivo metastasis models.
  • RNA immunoprecipitation and Western blotting to determine molecular interactions.

Main Results:

  • Identification of circURI1, back-spliced from the URI1 gene, with significantly higher expression in GC tissues.
  • CircURI1 demonstrated inhibitory effects on GC cell migration, invasion, and metastasis in vitro and in vivo.
  • Mechanistic studies revealed that circURI1 directly interacts with hnRNPM, modulating alternative splicing of genes critical for cell migration.

Conclusions:

  • CircURI1 acts as a tumor suppressor in gastric cancer by inhibiting metastasis.
  • The circURI1-hnRNPM interaction and subsequent modulation of alternative splicing represent a novel mechanism in circRNA-mediated cancer regulation.
  • This study expands the understanding of circRNA functions in gastric cancer and offers potential therapeutic targets.
Keywords:
alternative splicingcircURI1gastric cancerhnRNPMmetastasis

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