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LncRNA MEG3 negatively modified osteosarcoma development through regulation of miR‐361‐5p and FoxM1

Bin Shen,N. Zhou,Tao Hu,Weidong Zhao,Desheng Wu,Shanjin Wang

Published 2019 in Journal of Cellular Physiology

ABSTRACT

This study was aimed to figure out whether long noncoding RNA MEG3/miR‐361‐5p/FoxM1 signaling would contribute to improved proliferation and metastasis of osteosarcoma cells. We altogether collected 204 pairs of osteosarcoma tissues and adjacent normal tissues, and obtained four human osteosarcoma cell lines. Then pcDNA3.1‐MEG3, si‐MEG3, miR‐361‐5p mimic, miR‐361‐5p inhibitor, pcDNA3.1‐FoxM1, si‐FoxM1, and negative control (NC) were, respectively, transfected into the osteosarcoma cells. Furthermore, real time polymerase chain reaction was utilized to determine the mRNA expressions of maternally expressed gene 3 (MEG3) and miR‐361‐5p, and western blot analysis was applied for determining the FoxM1 expression. Besides, dual luciferase reporter gene assay was adopted to verify if MEG3 can be directly targeted by miR‐361‐5p. Finally, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide, colony formation assay, flow cytometry, wound healing assay, and transwell assay were conducted to investigate the influence of MEG3, miR‐361‐5p, and FoxM1 expressions on the viability, proliferation, apoptosis, migration, and invasion of osteosarcoma cells. MEG3 and miR‐361‐5p were observed to be significantly downregulated within both osteosarcoma tissues and cell lines, whereas FoxM1 was upregulated in osteosarcoma tissues and cell lines (p < 0.05). MEG3 directly bound to miR‐361‐5p, and significantly upgraded its expression (p < 0.05). The upregulated MEG3 and miR‐361‐5p or the downregulated FoxM1 appeared to substantially inhibit proliferation, migration, and invasion of osteosarcoma cells (p < 0.05). Finally, the proliferation, migration, invasion, and motility of osteosarcoma cells within the miR‐NC + pcDNA3.1‐FoxM1 group and pcDNA + pcDNA‐FoxM1 group were markedly promoted when compared with the miR‐361‐5p mimic group and pcDNA3.1‐MEG3 group (p < 0.05). The MEG3/miR‐361‐5p/FoxM1 axis could potentially serve as therapeutic targets or diagnostic biomarkers for osteosarcoma.

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