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下调 抑制血管瘤细胞增殖和侵袭,通过 Notch 信号通路介导促进细胞凋亡。

Knockdown of inhibits cell proliferation and invasion, but promotes cell apoptosis in hemangioma, via ‑induced mediation of the Notch signaling pathway.

机构信息

Department of General Surgery II (Department of Plastic Surgery), Affiliated Hospital of Hebei University of Engineering, Hebei, Handan 056002, P.R. China.

Department of Plastic Surgery, Handan Seventh Hospital, Hebei, Handan 056001, P.R. China.

出版信息

Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12512. Epub 2021 Oct 29.

Abstract

As a member of the long non‑coding (lnc)RNA family, lncRNA maternally expressed 8, small nucleolar RNA host gene (), 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 on human hemangioma endothelial cell (HemEC) proliferation, apoptosis and invasion, in addition to determining the underlying molecular mechanism. The knockdown of was achieved by transfecting small interfering (si)RNA into HemECs, while the combined knockdown of knockdown and microRNA (miR)‑203 was established by co‑transfecting siRNA and a miR‑203 inhibitor into HemECs. The cell proliferation, apoptosis and invasion and the expression levels of miR‑34a, , 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 significantly inhibited proliferation (P<0.05) and invasion (P<0.05), but promoted apoptosis (P<0.01) in HemECs. Furthermore, knockdown upregulated (P<0.01) expression, but did not alter or expression (both P>0.05). Subsequent experiments revealed that silencing exerted no significant effect on the expression levels of (P>0.05) in HemECs. In addition, silencing increased cell proliferation (P<0.05) and invasion (P<0.01), but suppressed apoptosis (P<0.05). silencing also reversed the effect of knockdown on the proliferation (P<0.05), apoptosis (P<0.001) and invasion (P<0.01) of HemECs. Moreover, knockdown downregulated jagged canonical notch ligand 1 (JAG1; P<0.05) and Notch1 (P<0.05) expression levels, while silencing upregulated JAG1 (P<0.01) and Notch1 (P<0.01) expression levels and reversed the effects of knockdown on JAG1 (P<0.01) and Notch1 (P<0.01) expression in HemECs. In conclusion, the findings of the present study suggested that knockdown may inhibit cell proliferation and invasion, but promote cell apoptosis in hemangioma via ‑induced mediation of the Notch signaling pathway.

摘要

作为长链非编码 RNA(lncRNA)家族的一员,lncRNA 母系表达 8,小核仁 RNA 宿主基因(),已被报道在多种恶性肿瘤中发挥致癌作用,包括肝细胞癌、非小细胞肺癌和胰腺癌。本研究旨在探讨敲低 lncRNA 对人血管内皮细胞瘤(HemEC)增殖、凋亡和侵袭的影响,并确定其潜在的分子机制。通过转染小干扰(si)RNA 到 HemEC 中实现了 lncRNA 的敲低,而通过共转染 siRNA 和 miR-203 抑制剂到 HemEC 中建立了 lncRNA 与 microRNA(miR)-203 的联合敲低。通过 CCK-8 试剂盒、流式细胞术、Transwell、逆转录定量 PCR 和 Western blot 检测细胞增殖、凋亡和侵袭以及 miR-34a、、和 Notch 信号通路相关因子的表达水平。结果显示,敲低 lncRNA 显著抑制了 HemEC 的增殖(P<0.05)和侵袭(P<0.05),但促进了凋亡(P<0.01)。此外,敲低 lncRNA 显著上调(P<0.01)表达,但不改变(均 P>0.05)或(均 P>0.05)表达。后续实验表明,沉默对 HemEC 中(P>0.05)的表达水平没有显著影响。此外,沉默增加了细胞增殖(P<0.05)和侵袭(P<0.01),但抑制了凋亡(P<0.05)。沉默还逆转了敲低 lncRNA 对 HemEC 增殖(P<0.05)、凋亡(P<0.001)和侵袭(P<0.01)的影响。此外,敲低 lncRNA 下调 Jagged 经典 Notch 配体 1(JAG1;P<0.05)和 Notch1(P<0.05)表达水平,而沉默上调 JAG1(P<0.01)和 Notch1(P<0.01)表达水平,并逆转了敲低 lncRNA 对 HemEC 中 JAG1(P<0.01)和 Notch1(P<0.01)表达的影响。综上所述,本研究结果表明,通过 - Notch 信号通路介导,敲低 lncRNA 可能抑制血管内皮细胞瘤增殖和侵袭,促进细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fef/8569514/e49868346d01/mmr-24-06-12512-g00.jpg

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