MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1.
10.1007/s13238-014-0093-5
- Author:
Mingxu SONG
1
;
Yuan YIN
;
Jiwei ZHANG
;
Binbin ZHANG
;
Zehua BIAN
;
Chao QUAN
;
Leyuan ZHOU
;
Yaling HU
;
Qifeng WANG
;
Shujuan NI
;
Bojian FEI
;
Weili WANG
;
Xiang DU
;
Dong HUA
;
Zhaohui HUANG
Author Information
1. Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Base Sequence;
Cell Line, Tumor;
Cell Movement;
genetics;
Colorectal Neoplasms;
genetics;
pathology;
therapy;
Down-Regulation;
Female;
Gene Expression Profiling;
Gene Expression Regulation, Neoplastic;
HCT116 Cells;
HEK293 Cells;
Humans;
Male;
Mice, Inbred BALB C;
Mice, Nude;
MicroRNAs;
genetics;
Middle Aged;
Neoplasm Invasiveness;
RNA Interference;
Receptor, Notch1;
genetics;
metabolism;
Receptors, Autocrine Motility Factor;
genetics;
metabolism;
Reverse Transcriptase Polymerase Chain Reaction;
Sequence Homology, Nucleic Acid;
Survival Analysis;
Xenograft Model Antitumor Assays
- From:
Protein & Cell
2014;5(11):851-861
- CountryChina
- Language:English
-
Abstract:
MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.
