title: Overexpression of miR-499-5p inhibits non-small cell lung cancer proliferation and metastasis by targeting VAV3.
abstract: Dysregulation of miRNAs is reported to be involved in the invasion and metastasis of lung cancer. Previous studies showed that low serum miR-499 expression was associated with advanced TNM stage and poor prognosis. The present study is carried out to evaluate the biological functions of miR-499-5p in lung cancer. We demonstrated that miR-499-5p was significantly reduced in NSCLC tissues and correlated with poor clinical outcomes. Overexpression of miR-499-5p inhibited cell proliferation and induced apoptosis in vitro and in vivo. Furthermore, miR-499-5p overexpression also inhibited NSCLC metastasis in vitro and in vivo. Using bioinformatics tools, we identified VAV3 as a candidate target of miR-499-5p, and demonstrated that restoration of miR-499-5p expression in NSCLC cells downregulated VAV3 expression while inhibition of miR-499-5p upregulated VAV3 expression. Luciferase reporter assays showed that miR-499-5p targeted 3'-UTR of VAV3. Moreover, cancer growth, proliferation and metastasis were decreased and apoptosis was increased after VAV3 blockage induced by miR-499-5p overexpression. We conclude that miR-499-5p functions as a tumor suppressor by targeting VAV3. This finding may provide a therapeutic approach for future treatment of NSCLC.
authors.affiliation: Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shenjun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University, Shanghai 200072, China.|Institute of Biochemistry and Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Lin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human