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