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Updated: Feb 3, 2026

Identification of Circular RNAs using RNA Sequencing
08:25

Identification of Circular RNAs using RNA Sequencing

Published on: November 14, 2019

12.8K

Circular RNA circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes

Yajun Chen1, Feng Yang2, Erhu Fang2

  • 1Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei Province, China.

Cell Death and Differentiation
|October 21, 2018
PubMed

Insights

A novel circular RNA (circRNA) called circAGO2 promotes cancer by interfering with Argonaute 2 (AGO2) and microRNA (miRNA) silencing. Targeting circAGO2 or its interaction with HuR protein inhibits tumor growth and spread.

Area of Science:

  • Molecular Biology
  • Oncology
  • RNA Biology

Background:

  • Argonaute 2 (AGO2) is crucial for microRNA (miRNA)-mediated gene silencing and implicated in cancer.
  • The regulatory mechanisms governing AGO2 function in cancer remain incompletely understood.
  • Circular RNAs (circRNAs) are emerging as significant players in various biological processes, including cancer.

Purpose of the Study:

  • To identify and characterize novel regulators of AGO2 function in cancer.
  • To investigate the role of circRNAs in modulating AGO2-miRNA complexes.
  • To explore circAGO2 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Identification and characterization of circAGO2 derived from the AGO2 gene.
  • Expression analysis of circAGO2 in various cancer types (gastric, colon, prostate, neuroblastoma).
  • In vitro and in vivo assays to assess the functional role of circAGO2 in cancer cell growth, invasion, and metastasis.
  • Mechanistic studies involving RNA-protein interaction assays (e.g., RIP-qPCR) to investigate the interaction between circAGO2 and HuR.
  • Therapeutic interventions using shRNA targeting circAGO2 and cell-penetrating peptides to block circAGO2-HuR interaction in preclinical models.

Main Results:

  • CircAGO2 is significantly upregulated in multiple cancers and correlates with poor patient prognosis.
  • CircAGO2 promotes cancer cell proliferation, invasion, and metastasis both in vitro and in vivo.
  • CircAGO2 interacts with HuR protein, enhancing its activity and leading to reduced AGO2 binding and impaired miRNA-mediated gene silencing.
  • Targeting circAGO2 with shRNA or blocking its interaction with HuR using peptides effectively suppresses tumor growth and aggressiveness in preclinical models.

Conclusions:

  • Oncogenic circAGO2 acts as a novel regulator of AGO2-miRNA complexes in cancer progression.
  • CircAGO2 drives tumorigenesis and metastasis by facilitating HuR-mediated repression of AGO2/miRNA silencing.
  • CircAGO2 and its interaction with HuR represent promising therapeutic targets for inhibiting cancer growth and spread.

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