OncoTargets and Therapy (Oct 2020)

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

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

Journal volume & issue
Vol. Volume 13
pp. 10257 – 10266

Abstract

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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 workCorrespondence: Jiahui Du Email [email protected]: 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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