Silencing long non-coding RNA MEG8 inhibits the proliferation and induces the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis

• Published in: Biochemical and biophysical research communications Vol. 556; pp. 72 - 78
• Main Authors: Ma, Qingjie, Dai, Xiaolin, Lu, Weiwei, Qu, Xiaowen, Liu, Na, Zhu, Chongtao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.06.2021
• Subjects: Amino Acid Transport System y+ - genetics; Amino Acid Transport System y+ - metabolism; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Base Sequence; carcinogenesis; Cell Proliferation - drug effects; Cell Proliferation - genetics; cell viability; Cyclohexylamines - pharmacology; Down-Regulation; Endothelial Cells - metabolism; Endothelial Cells - pathology; Ferroptosis; Ferroptosis - drug effects; Ferroptosis - genetics; Gene Silencing - drug effects; Hemangioma; Hemangioma - genetics; Humans; Long non-coding RNA MEG8; MicroRNAs - genetics; MicroRNAs - metabolism; miR-497-5p; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; non-coding RNA; NOTCH2; Phenylenediamines - pharmacology; Phospholipid Hydroperoxide Glutathione Peroxidase - genetics; Phospholipid Hydroperoxide Glutathione Peroxidase - metabolism; protein content; Quinoxalines - pharmacology; Receptor, Notch2 - biosynthesis; Receptor, Notch2 - genetics; Receptor, Notch2 - metabolism; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Small Interfering - genetics; Spiro Compounds - pharmacology; NOTCH2; Ferroptosis; Hemangioma; Long non-coding RNA MEG8; miR-497-5p
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2021.03.132

Even though long non-coding RNA (lncRNA) MEG8 plays vital roles in carcinogenesis of malignances, its roles and mechanisms in hemangioma remain unknown. Therefore, we evaluate the oncogenic roles of MEG8 in hemangioma. Small interfering RNA (siRNA)-mediated depletion of MEG8 inhibited the proliferation and increased MDA level in human hemangioma endothelial cells (HemECs). The inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) abolished the MEG8 silence induced cell viability loss. Knockdown of MEG8 increased the miR-497-5p expression and reduced the mRNA and protein levels of NOTCH2. Using a dual-luciferase assay, we confirmed the binding between MEG8 and miR-497-5p, and between the miR-497-5p and 3′UTR of NOTCH2. We further found that silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. Importantly, blocking miR-497-5p abrogated the effects of MEG8 loss on cell viability, MDA level and expression levels of NOTCH2, SLC7A11 and GPX4 in HemECs. Taken together, our results suggested that knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. •Depletion of MEG8 inhibited the proliferation and increased MDA level in human hemangioma endothelial cells (HemECs).•The inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) abolished the MEG8 silence induced cell viability loss.•MEG8 positively regulated NOTCH2 by sponging miR-497-5p.•Silencing MEG8 decreased SLC7A11 and GPX4 expression both in mRNA and protein level and had no effect on AIFM2.