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In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
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In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions

Published on: October 21, 2022

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Intragenic antagonistic roles of protein and circRNA in tumorigenesis

Jlenia Guarnerio1,2, Yang Zhang1, Giulia Cheloni1

  • 1Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Cell Research
|June 19, 2019
PubMed

Insights

A novel circular RNA, circPOK, acts as a cancer-promoting oncogene, distinct from its tumor-suppressing linear counterpart. This discovery reveals a new regulatory unit, the iRegulon, with opposing functions in cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Circular RNAs (circRNAs) are emerging regulators in cancer development.
  • The Zbtb7a gene produces both linear (Pokemon protein) and circular (circPOK) RNA transcripts.
  • Aberrant circRNA expression is linked to various pathologies, including cancer.

Purpose of the Study:

  • To characterize the novel circRNA, circPOK, derived from the Zbtb7a gene.
  • To elucidate the distinct functions of circPOK and its linear counterpart in mesenchymal tumors.
  • To identify novel regulatory mechanisms in cancer pathogenesis.

Main Methods:

  • RNA sequencing and bioinformatics analysis to identify and characterize circPOK.
  • Functional assays to determine the oncogenic role of circPOK.
  • Investigation of circPOK's interaction with the ILF2/3 complex.
  • Analysis of Pokemon protein and circPOK expression in cancer tissues.

Main Results:

  • circPOK functions as a non-coding RNA with proto-oncogenic activity in mesenchymal tumors.
  • circPOK promotes proliferation and angiogenesis by co-activating the ILF2/3 complex.
  • Pokemon protein, encoded by the linear transcript, acts as a tumor suppressor.
  • Expression of Pokemon protein and circPOK is uncoupled in cancer due to differential post-transcriptional regulation.

Conclusions:

  • A novel genetic unit, the iRegulon, generates distinct circular and linear RNA products with opposing functions.
  • circPOK represents a new class of oncogenic circRNAs.
  • Aberrant expression of iRegulons contributes to disease pathogenesis, highlighting new therapeutic targets.

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