OBJECTIVE: The present study aimed to determine the expression of long non-coding RNA (lncRNA) FOXD3 antisense RNA 1 (FOXD3-AS1) in lung cancer tissues and to explore its underlying mechanisms in mediating non-small cell lung cancer (NSCLC) progression.
MATERIALS AND METHODS: Gene expression levels were determined by quantitative real-time PCR; lung cancer cell proliferation and invasion were determined by in vitro functional assays; protein levels were determined by Western blot assay; xenograft nude mice model was used to evaluate the in vivo tumor growth of lung cancer cells; Luciferase reporter assay determined the interactions among FOXD3-AS1, miR-127-3p, and mediator complex subunit 28 (MED28).
RESULTS: Data mining and analysis of the clinical sample showed that FOXD3-AS1 expression was significantly up-regulated in lung cancer tissues. In vitro functional assays demonstrated that FOXD3-AS1 overexpression promoted NSCLC cell proliferation and invasion, while FOXD3-AS1 knockdown exerted tumor-suppressive effects on NSCLC cells. Moreover, FOXD3-AS1 interacted with miR-127-3p by acting as a competing endogenous RNA to suppress miR-127-3p expression, while miR-127-3p repressed MED28 expression by targeting MED28 3’ untranslated region in NSCLC cells. Mechanistically, the oncogenic effects of FOXD3-AS1 overexpression were significantly attenuated by miR-127-3p overexpression and MED28 knockdown in NSCLC cells. In the xenograft mice model, FOXD3-AS1 knockdown suppressed in vivo tumor growth of A549 cells, and also up-regulated miR-127-3p expression and repressed MED28 expression in the xenograft tumors. In the clinical aspect, the downregulation of miR-127-3p and up-regulation of MED28 were respectively detected in lung cancer tissues.
CONCLUSIONS: Our findings provided new evidence that the FOXD3-AS1 regulated NSCLC progression via targeting the miR-127-3p/MED28 axis.
Free PDF Download
To cite this article
Z.-L. Zeng, H.-K. Zhu, L.-F. He, X. Xu, A. Xie, E.-K. Zheng, J.-J. Ni, J.-T. Liu, G.-F. Zhao
Highly expressed lncRNA FOXD3-AS1 promotes non-small cell lung cancer progression via regulating miR-127-3p/mediator complex subunit 28 axis
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 5