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: Ming Li, Shenjun Zhang, Ning Wu, Liang Wu, Changhui Wang, Yinping Lin
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 23100 (Mar 14 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26972445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• 3' Untranslated Regions
• MIRN499 microRNA, human
• MicroRNAs
• Proto-Oncogene Proteins c-vav
• VAV3 protein, human

Topics

• 3' Untranslated Regions (genetics)
• A549 Cells
• Animals
• Apoptosis (genetics)
• Base Sequence
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Cycle (genetics)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice, Nude
• MicroRNAs (genetics)
• Neoplasm Metastasis
• Proto-Oncogene Proteins c-vav (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Homology, Nucleic Acid
• Transplantation, Heterologous