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Updated: Oct 29, 2025

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
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HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein

Yan Li1, Bing Chen1, Jingjing Zhao1

  • 1Department of Integrative Oncology Fudan University Shanghai Cancer Center Shanghai Key Laboratory of Medical Epigenetics Institutes of Biomedical Sciences Shanghai Medical College Fudan University Shanghai 200032 China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 14, 2021
PubMed

Insights

A novel circular RNA, circARHGAP35, derived from a tumor suppressor gene, drives cancer progression by producing a truncated oncogenic protein. This circRNA is linked to poor patient survival, revealing a new cancer mechanism.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Biology

Background:

  • Circular RNAs (circRNAs) are prevalent but largely uncharacterized endogenous RNAs.
  • The tumor suppressor gene ARHGAP35 (P190-A) plays a role in cellular regulation.

Purpose of the Study:

  • To identify and characterize novel oncogenic circRNAs.
  • To elucidate the functional role and mechanism of circARHGAP35 in cancer.

Main Methods:

  • Identification of circARHGAP35 through back-splicing of ARHGAP35 gene.
  • Analysis of circARHGAP35 expression and function.
  • Investigation of circARHGAP35 protein interaction with TFII-I.
  • Assessment of HNRNPL's role in circARHGAP35 formation.
  • Clinical correlation analysis with patient survival data.

Main Results:

  • A novel oncogenic circRNA, circARHGAP35, was identified from the ARHGAP35 gene.
  • circARHGAP35 exhibits inverse expression and function compared to its linear counterpart.
  • circARHGAP35 encodes a truncated protein with oncogenic activity, promoting cancer progression via nuclear TFII-I interaction.
  • HNRNPL facilitates circARHGAP35 biogenesis.
  • High circARHGAP35 levels correlate with poor prognosis in cancer patients.

Conclusions:

  • circARHGAP35 is a novel oncogenic circRNA.
  • It represents a new mechanism of oncogene activation in cancer through truncated protein production.
  • circARHGAP35 serves as a potential biomarker for cancer prognosis.
Keywords:
ARHGAP35HNRNPLcancer progressioncircular RNAsoncogenic proteinstranslation

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