MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3
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Zhaowu Ma1,2,*, Teng Liu1,*, Wei Huang1, Hui Liu1, Hong-Mei Zhang1, Qiubai Li3, Zhichao Chen3, An-Yuan Guo1
1Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China
2Laboratory of Neuronal Network and Brain Diseases Modulation, School of Medicine, Yangtze University, Jingzhou, Hubei, 434023, China
3Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
*These authors contributed equally to this work
An-Yuan Guo, email: firstname.lastname@example.org
Zhaowu Ma, email: email@example.com
Keywords: microRNA, regulatory network, cancer, miR-142-5p, TGF-β pathway
Received: January 29, 2016 Accepted: September 12, 2016 Published: September 24, 2016
MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher’s exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo.life.hust.edu.cn/miR_path). As one of the miRNAs targeting many cancer related pathways, miR-142-5p potentially regulates the maximum number of genes in TGF-β signaling pathway. We experimentally confirmed that miR-142-5p directly targeted and suppressed SMAD3, a key component in TGF-β signaling. Ectopic overexpression of miR-142-5p significantly promoted tumor cell proliferation and inhibited apoptosis, while silencing of miR-142-5p inhibited the tumor cell proliferation and promoted apoptosis in vitro. These findings indicate that miR-142-5p plays as a negative regulator in TGF-β pathway by targeting SMAD3 and suppresses TGF-β-induced growth inhibition in cancer cells. Our study proved the feasibility of miRNA regulatory pathway analysis and shed light on combining bioinformatics with experiments in the research of complex diseases.
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