Circular RNA CircAGO2 Drives Cancer Progression Through Facilitating HuR-repressed Functions of AGO2-miRNA Complexes

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 Oct 21

PMID 30341421

Citations 175

Authors

Yajun Chen

Feng Yang

Erhu Fang

Wenjing Xiao

Hong Mei

Huanhuan Li

Dan Li

Huajie Song

Jianqun Wang

Mei Hong

Xiaojing Wang

Kai Huang

Liduan Zheng

Qiangsong Tong

Affiliations

Soon will be listed here.

Abstract

Argonaute 2 (AGO2), the core component of microRNA (miRNA)-induced silencing complex, plays a compelling role in tumorigenesis and aggressiveness. However, the mechanisms regulating the functions of AGO2 in cancer still remain elusive. Herein, we indentify one intronic circular RNA (circRNA) generated from AGO2 gene (circAGO2) as a novel regulator of AGO2-miRNA complexes and cancer progression. CircAGO2 is up-regulated in gastric cancer, colon cancer, prostate cancer, and neuroblastoma, and is associated with poor prognosis of patients. CircAGO2 promotes the growth, invasion, and metastasis of cancer cells in vitro and in vivo. Mechanistic studies reveal that circAGO2 physically interacts with human antigen R (HuR) protein to facilitate its activation and enrichment on the 3'-untranslated region of target genes, resulting in reduction of AGO2 binding and repression of AGO2/miRNA-mediated gene silencing associated with cancer progression. Pre-clinically, administration of lentivirus-mediated short hairpin RNA targeting circAGO2 inhibits the expression of downstream target genes, and suppresses the tumorigenesis and aggressiveness of xenografts in nude mice. In addition, blocking the interaction between circAGO2 and HuR by cell-penetrating inhibitory peptide represses the tumorigenesis and aggressiveness of cancer cells. Taken together, these results indicate that oncogenic circAGO2 drives cancer progression through facilitating HuR-repressed functions of AGO2-miRNA complexes.

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