Overexpression of miR-499-5p inhibits non-small cell lung cancer proliferation and metastasis by targeting VAV3
Authors: Ming Li
Changhui Wang
Liang Wu
Ning Wu
Yinping Lin
Shenjun Zhang
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: miR-499-5p; lung cancer; tumor suppressor; VAV3; metastasis
Affiliations: 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., Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China., Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China.

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. 

Retracted: Yes

PubPeer comments:
 There appear to be several image duplications within images in figures 3C, 3D, and 5C ![file] ![file] ![file] There are likely more, but I think the general pattern is clear. , 
 Thanks for your reminding, I ll check the raw data. , 
 Figure 2D appears to have a reused band. *** ![file] *** Inverse shows common background ![file] , 
 #1 ![file] , 
 Thank you for your questions. Students were in charged of the part of the Transwell and WB experiments and I should be responsible for this result. We are now checking the raw data. However, I think we should retract the paper. Thanks for your questions. We will handle it as soon as possible. , 
 #5 I agree that it is difficult to understand how these errors could occur by accident. However, it would be interesting to hear how the authors explain how this happened. , 
 Retracted [23 August 2021] . ---------------------- The Editors have retracted this Article. Several of the figures presented in this paper appear to contain duplications that are not compliant with the digital image and standards policy of the journal, specifically: - There appears to be partial overlap of the actin panels presented in Figure 2A - There appears to be a high level of similarity between the actin bands presented in Figure 3A - There appears to be duplication within the panels presented in Figure 3C - There appears to be duplication within and between the panels presented in Figure 3D - There appears to be duplication of the panels for u03b2-actin in Figure 4C In addition, the last author has stated they were not able to locate all the original data files. The Editors therefore no longer have confidence in the reliability of the data reported in the Article. The authors have not responded to correspondence regarding this retraction. , 
 Fig 5A. ![file] Reworked versions of previously-published images. - *[left]* Fig 1C from  MiR-25 promotes hepatocellular carcinoma cell growth, migration and invasion by inhibiting RhoGDI1 ([Wang et al 2015] ). - *[right]* Fig 2a from  Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells ([Wang et al 2013] ). ![file] ,