MiR-22 Has a Potent Anti-tumour Role with Therapeutic Potential in Acute Myeloid Leukaemia

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 27

PMID 27116251

Citations 86

Authors

Xi Jiang

Chao Hu

Stephen Arnovitz

Jason Bugno

Miao Yu

Zhixiang Zuo

Ping Chen

Hao Huang

Bryan Ulrich

Sandeep Gurbuxani

Hengyou Weng

Jennifer Strong

Yungui Wang

Yuanyuan Li

Justin Salat

Shenglai Li

Abdel G Elkahloun

Yang Yang

Mary Beth Neilly

Richard A Larson

Michelle M Le Beau

Tobias Herold

Stefan K Bohlander

Paul P Liu

Jiwang Zhang

Zejuan Li

Chuan He

Jie Jin

Seungpyo Hong

Jianjun Chen

Affiliations

Soon will be listed here.

Abstract

MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy.

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