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.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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