title: MiR-374a suppresses lung adenocarcinoma cell proliferation and invasion by targeting TGFA gene expression.
abstract: Aberrant expression of miR-374a has been reported in several types of human cancers, including lung cancer. However, the functional significance and molecular mechanisms underlying the role of miR-374a in lung cancer remain largely unknown. We found that the expression of miR-374a was significantly downregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues in samples included in The Cancer Genome Atlas. Functional studies revealed that overexpression of miR-374a led to inhibition of lung adenocarcinoma cell proliferation, migration and invasion and that miR-374a negatively regulated transforming growth factor-alpha (TGFA) gene expression by directly targeting the 3'-UTR of TGFA mRNA. Treating lung adenocarcinoma cells with TGF-α neutralizing antibody resulted in suppression of cell proliferation and invasion, which mimicked the action of miR-374a. Additionally, TGFA gene expression was significantly higher in tumor tissues compared to adjacent normal tissue and high TGFA gene expression strongly correlated with poor survival in patients with lung adenocarcinoma. Taken together, our studies suggest that miR-374a suppresses lung adenocarcinoma cell proliferation and invasion via targeting TGFA gene expression. Our findings may provide novel treatment strategies for lung adenocarcinoma patients.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA and Department of Radiation Oncology, Qilu Hospital Affiliated to Shandong University, 107#, Wenhua Xi Road, Jinan 250012, Shandong, China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA and.
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA and qiuyin.cai@vanderbilt.edu.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000502:physiology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D057134:Antibodies, Neutralizing; C587995:MIRN374 microRNA 374, human; D035683:MicroRNAs; C587886:TGFA protein, human; D016211:Transforming Growth Factor alpha