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

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.

Sp1-activated Long Noncoding RNA NCK1-AS1&nbsp;Facilitates Cell Growth of Breast Cancer via Sponging miR-361-5p&nbsp;

“…For instance, lncRNA SBF2-AS1 mediated FOXM1 upregulation promotes cell proliferation in cervical cancer by sequestering miR-361-5p (26). LncRNA MEG3 obstructed osteosarcoma cell growth by modifying miR-361-5p and FoxM1 (27). Nevertheless, the molecular mechanism of miR-361-5p in BC are elusive.…”

Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)

“…Sahin et al (43) showed that MEG3 attenuates proliferation and migration of OS cells through directly interacting with miR-664a. In addition, MEG3 can directly bind to miR-361-5p and increase its expression, downregulating the expression of FoxM1 (44). In this case, MEG3 abrogates development of OS via a miR-361-5p/FoxM1 axis instead of acting as a ceRNA.…”

LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972

“…Several of these lncRNAs are implicated in the downregulation of target gene expression (Yang et al, 2019), while others have been found to upregulate the expression of target genes (Li et al, 2013;Deng et al, 2019). An increasing number of studies indicate that lncRNAs play an important role in osteosarcoma development by affecting the following processes: cell proliferation, cellular invasion, migration, metastasis, stemness, fate, and EMT (Huang et al, 2018;Shen et al, 2019). Moreover, several lncRNAs are being actively investigated as prognostic markers for this disease (Chen et al, 2018;.…”

“…A mechanism of interest, which has been reported on several times, involves lncRNAs working as competing endogenous RNAs (ceRNA), in which the lncRNA can act as a sponge for specific miRNAs and indirectly regulate the expression of tumorrelated genes Deng et al, 2019;Shen et al, 2019). Tp53, a well-known and extensively studied gene in tumors, was first reported to exhibit intron 1 rearrangement (Masuda et al, 1987).…”