Knockdown of lncRNA MEG8 inhibits cell proliferation and invasion, but promotes cell apoptosis in hemangioma, via miR-203-induced mediation of the Notch signaling pathway

As a member of the long non-coding (lnc)RNA family, lncRNA maternally expressed 8, small nucleolar RNA host gene (MEG8), has been reported to serve an oncogenic role in several types of malignancies, including hepatocellular carcinoma, non-small cell lung cancer and pancreatic cancer. The current study aimed to investigate the effect of the knockdown of MEG8 on human hemangioma endothelial cell (HemEC) proliferation, apoptosis and invasion, in addition to determining the underlying molecular mechanism. The knockdown of lncRNA MEG8 was achieved by transfecting lncRNA MEG8 small interfering (si)RNA into HemECs, while the combined knockdown of lncRNA MEG8 knockdown and microRNA (miR)-203 was established by co-transfecting lncRNA MEG8 siRNA and a miR-203 inhibitor into HemECs. The cell proliferation, apoptosis and invasion and the expression levels of miR-34a, miR-200b, miR-200b and Notch signaling pathway-related factors were detected via CCK-8 Kit, flow cytometry, Transwell, reverse transcription-quantitative PCR and western blot assay, respectively. The knockdown of lncRNA MEG8 significantly inhibited proliferation (P<0.05) and invasion (P<0.05), but promoted apoptosis (P<0.01) in HemECs. Furthermore, lncRNA MEG8 knockdown upregulated miR-203 (P<0.01) expression, but did not alter miR-34a or miR-200b expression (both P>0.05). Subsequent experiments revealed that miR-203 silencing exerted no significant effect on the expression levels of lncRNA MEG8 (P>0.05) in HemECs. In addition, miR-203 silencing increased cell proliferation (P<0.05) and invasion (P<0.01), but suppressed apoptosis (P<0.05). miR-203 silencing also reversed the effect of lncRNA MEG8 knockdown on the proliferation (P<0.05), apoptosis (P<0.001) and invasion (P<0.01) of HemECs. Moreover, lncRNA MEG8 knockdown downregulated jagged canonical notch ligand 1 (JAG1; P<0.05) and Notch1 (P<0.05) expression levels, while miR-203 silencing upregulated JAG1 (P<0.01) and Notch1 (P<0.01) expression levels and reversed the effects of lncRNA MEG8 knockdown on JAG1 (P<0.01) and Notch1 (P<0.01) expression in HemECs. In conclusion, the findings of the present study suggested that lncRNA MEG8 knockdown may inhibit cell proliferation and invasion, but promote cell apoptosis in hemangioma via miR-203-induced mediation of the Notch signaling pathway.

Automated summary

The knockdown of lncRNA MEG8 inhibited cell proliferation and invasion, while promoting apoptosis in HemECs. It upregulated the expression of miR-203, but had no effect on miR-34a or miR-200b. Silencing of miR-203 increased cell proliferation and invasion, while reducing apoptosis, and reversed the effects of lncRNA MEG8 knockdown on HemECs. Additionally, lncRNA MEG8 knockdown downregulated JAG1 and Notch1 expression levels, while miR-203 silencing upregulated JAG1 and Notch1 expression and reversed the effects of lncRNA MEG8 knockdown on JAG1 and Notch1 expression in HemECs.