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miR-519d-3p Overexpression Inhibits P38 and PI3K/AKT Pathway via Targeting VEGFA to Attenuate the Malignant Biological Behavior of Non-Small Cell Lung Cancer

Authors Zhang G, Hu Y, Yuan W, Qiu H, Yu H, Du J

Received 6 March 2020

Accepted for publication 25 August 2020

Published 12 October 2020 Volume 2020:13 Pages 10257—10266

DOI https://doi.org/10.2147/OTT.S252795

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Federico Perche


Guangzhao Zhang,1,* Yanlei Hu,2,* Wuying Yuan,1 Hongli Qiu,1 Haifeng Yu,1 Jiahui Du1

1Department of Minimally Invasive Surgery, Henan Chest Hospital, Zhengzhou, Henan 450003, People’s Republic of China; 2Department of Cardiovascular Surgery, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan 451464, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jiahui Du Email zhanggz45@sina.com

Background: Non-small cell lung cancer (NSCLC) is a heterogeneous tumor that accounts for approximately 85% of all lung cancer cases worldwide. microRNAs (miRNAs) are believed to play an important role in regulating a variety of biological processes, including immunity and cancer. We investigated the effect of miR-519d-3p on the mitigation of NSCLC in vitro and in vivo.
Methods: RT-PCR or immunohistochemical assays were used to assess the expression of miR-519d-3p. Colony formation, flow cytometry, and transwell assay were respectively used to detect proliferation, apoptosis, and invasion of A549 and NCI-H661 cell lines. Luciferase reporter assay was used to verify targeting the relationship between mir-519d-3p and VEGFA. Western blot was used to examine the expression of Ki67, caspase-3, E-cadherin, N-cadherin, VEGF, P38, and PI3K/AKT. Animal models were established by BABL/c mice to research the effect of mir-519d-3p overexpression in vivo.
Results: In vitro, miR-519d-3p overexpression inhibited A549 and NCI-H661 cells proliferation, invasion, and also promoted apoptosis. In addition, miR-519d-3p overexpression downregulated VEGFA expression and decreased the P38 and PI3K/AKT phosphorylation level. In vivo, miR-519d-3p overexpression significantly restrained tumor volume (2087± 265 mm3 vs 599± 135 mm3, *P<  0.05) and tumor weight (0.45± 0.08 g vs 0.13± 0.06 g, *P< 0.05) compared with the control group. Overexpression of miR-519d-3p downregulated levels of Ki67 and N-cadherin significantly.
Conclusion: The data indicated that miR-519d-3p could be a novel therapy or adjuvant against NSCLC.

Keywords: miR-519d-3p, invasion, non-small cell lung cancer, A549 cells, apoptosis

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