MiR-625 Inhibits Tumor Cell Invasion, Migration and EMT by Negatively Regulating the Expression of Resistin in Non-Small Cell Lung
Authors Zhao Y, Zheng R, Ning D, Xie F
Received 3 February 2020
Accepted for publication 27 April 2020
Published 3 June 2020 Volume 2020:12 Pages 4171—4180
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Ahmet Emre Eskazan
Yongsheng Zhao,1,* Renyan Zheng,2,* Dong Ning,1 Fei Xie1
1Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan; 2Department of Integrated Western and Chinese Colorectal and Anal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan
*These authors contributed equally to this work
Correspondence: Yongsheng Zhao Tel +86 13551910279
Purpose: To investigate the role of miR-625 on the invasion, migration, and epithelial–mesenchymal transition (EMT) of non-small cell lung carcinoma (NSCLC) cells, and the related mechanisms.
Materials and Methods: The expression levels of miR-625 and Resistin mRNA in 80 pairs of NSCLC and para-cancerous lung tissues were analyzed by RT-PCR. The relationship between miR-625 and Resistin was predicted by bioinformatics and verified by a dual-luciferase gene reporter assay. NSCLC cells were transfected with Resistin plasmids, si-Resistin plasmids, miR-625 mimics, or miR-625 inhibitors, and proliferation, invasion, and migration were determined by CCK-8, Transwell, and wound scratch assays, respectively. EMT-related proteins were determined by Western blot assay. A xenograft model of NSCLC was established in nude mice to validate the in vitro findings.
Results: MiR-625 was significantly downregulated in NSCLC tissue compared to paired para-cancerous lung tissues, while Resistin was markedly increased in tumor tissue. The expression levels of miR-625 and Resistin were negatively correlated in NSCLC tissues, and high levels of Resistin correlated with greater tumor differentiation, more advanced clinical staging, and lymph node metastasis. Furthermore, Resistin was a target gene of miR-625, and the latter downregulated Resistin to inhibit the EMT, proliferation, invasion, and migration of NSCLC cells in vitro, likely via the PI3K/AKT/Snail signaling pathway. Finally, miR-625 also inhibited the tumorigenic effect of NSCLC cells in vivo by downregulating Resistin.
Conclusion: MiR-625 acts as a tumor suppressor in NSCLC and inhibits tumor cell invasion and metastasis by blocking the Resistin/PI3K/AKT/Snail pathway and by decreasing EMT.
Keywords: miR-625, resistin, EMT, invasion, migration, PI3K/AKT/snail
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