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MiR-21-5p promotes the progression of non-small-cell lung cancer by regulating the expression of SMAD7

Authors Li X, Wu X

Received 26 April 2018

Accepted for publication 19 September 2018

Published 28 November 2018 Volume 2018:11 Pages 8445—8454

DOI https://doi.org/10.2147/OTT.S172393

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly


Xiangpan Li,1 Xiaofei Wu2

1Department of Oncology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei Province, People’s Republic of China; 2Department of Neurology, Chinese People’s Liberation Army, Wuhan General Hospital, Wuchang District, Wuhan, Hubei Province, People’s Republic of China

Objective: The objective of this study was to detect the expression of MiR-21-5p in non-small-cell lung cancer (NSCLC) tissues, and to investigate the effect of its expression on the progression of NSCLC.
Methods: Real-time fluorescent quantitative PCR was used to detect the relative expression of MiR-21-5p in 118 NSCLC tumor tissues to their adjacent normal tissues. The expressions of SMAD7, MMP-9, E-cadherin, and vimentin proteins were detected by Western blotting or immunohistochemistry. Cell colony formation, scratch, and Transwell assays were used to detect the proliferation, migration, and invasion ability of A549 cells, respectively.
Results: MiR-21-5p was highly expressed in the tumor tissues of NSCLC patients, and its expression was significantly correlated with the clinical classification of NSCLC patients (χ2=7.154, P=0.007), tumor size (χ2=4.372, P=0.037), differentiation (χ2=13.713, P=0.001), lymph node metastasis (χ2=5.101, P=0.024), distant metastasis (χ2=12.599, P=0.000), and TNM stage (χ2=6.344, P=0.012), whereas it was positively correlated with the expression of SMAD7 protein (r=0.669, P<0.05). The results of the luciferase gene reporter system showed that MiR-21-5p targeted and promoted the expression of SMAD7 gene, which enhanced NSCLC cell proliferation. Furthermore, MiR-21-5p promoted the expressions of MMP-9 and vimentin proteins as well as inhibited the expression of E-cadherin protein, which is associated with an elevated SMAD7 protein expression and enhanced the invasion/migration ability of NSCLC cells.
Conclusion: MiR-21-5p was highly expressed in NSCLC tumor tissues, and its high expression could promote NSCLC progression by targeting the expression of SMAD7.

Keywords: MiR-21-5p, SMAD7, non-small-cell lung cancer, progression, MMP-9, E-cadherin

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