MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1

miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e102602-e102602
Main Authors: Gu, Yixue, Cheng, Ye, Song, Ying, Zhang, Zhijie, Deng, Min, Wang, Chengkun, Zheng, Guopei, He, Zhimin
Format: Article
Language:English
Subjects:
Analysis of Variance
Bladder cancer
Blotting, Western
Breast cancer
Cancer
Carcinoma, Non-Small-Cell Lung - metabolism
Cell growth
Cell Line, Tumor
Cell Movement - genetics
Cell Movement - physiology
Cell Proliferation - genetics
Cell Proliferation - physiology
Colorectal cancer
Disease Progression
DNA Primers - genetics
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
Ectopic expression
Fibroblasts
Flow Cytometry
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Gene Silencing
Humans
Immunohistochemistry
Kinases
Luciferases
Lung cancer
Lung diseases
Medical prognosis
Medical research
Medicine and Health Sciences
Metastases
Metastasis
MicroRNAs
MicroRNAs - metabolism
miRNA
Molecular modelling
mRNA
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - physiopathology
Neoplasm Metastasis - genetics
Neoplasm Metastasis - physiopathology
Non-small cell lung carcinoma
Proteins
Real-Time Polymerase Chain Reaction
Regulators
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
Signal Transduction - physiology
Survival analysis
Therapeutic applications
Transcription factors
Tumorigenesis
Tumors
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Summary:miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0102602