MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells

Honghe Zhang; Jinlong Tang; Chen Li; Jianlu Kong; Jingyu Wang; Yihua Wu; Enping Xu; Maode Lai

doi:10.1016/j.canlet.2014.10.029

MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells

Cancer Lett. 2015 Jan 28;356(2 Pt B):781-90. doi: 10.1016/j.canlet.2014.10.029. Epub 2014 Oct 29.

Authors

Honghe Zhang¹, Jinlong Tang², Chen Li¹, Jianlu Kong¹, Jingyu Wang³, Yihua Wu⁴, Enping Xu¹, Maode Lai⁵

Affiliations

¹ Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, China.
² Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China; Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
³ Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China; Department of Pathology, The First Hospital of Jiaxing, Jiaxing, China.
⁴ Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China.
⁵ Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, China. Electronic address: [email protected].

PMID: 25449431
DOI: 10.1016/j.canlet.2014.10.029

Abstract

Autophagy has become one of the most important mechanisms of chemotherapy resistance by supporting the survival of tumor cells under metabolic and therapeutic stress. Here, we showed that miR-22 inhibited autophagy and promoted apoptosis to increase the sensitivity of colorectal cancer (CRC) cells to 5-fluorouracil (5-FU) treatment both in vitro and in vivo. B-cell translocation gene 1 (BTG1) was identified as a new target of miR-22, which could reverse the inhibition of autophagy induced by miR-22. Thus, miR-22 may function as an important switch between autophagy and apoptosis to regulate 5-FU sensitivity through post-transcriptional silencing of BTG1. Promisingly, miR-22 could be considered as both a predictor of 5-FU sensitivity for personalized treatment and a therapeutic target for colorectal cancer.

Keywords: 5-FU; Apoptosis; Autophagy; Colorectal cancer; MiR-22.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy
Adenocarcinoma / genetics
Adenocarcinoma / pathology
Animals
Antimetabolites, Antineoplastic / pharmacology
Apoptosis / drug effects*
Apoptosis Regulatory Proteins
Autophagy / drug effects*
Blotting, Western
Cell Proliferation / drug effects
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Drug Resistance, Neoplasm / genetics
Fluorouracil / pharmacology*
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Immunoenzyme Techniques
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Xenograft Model Antitumor Assays

Substances

Antimetabolites, Antineoplastic
Apoptosis Regulatory Proteins
MIRN22 microRNA, human
MicroRNAs
RNA, Messenger
Fluorouracil