Linc00152 敲低可使 Akt/mTOR 和 Notch1 通路失活，从而发挥其抗血管瘤作用。
Linc00152 knockdown inactivates the Akt/mTOR and Notch1 pathways to exert its anti-hemangioma effect.
机构信息
Department of Hemangioma and Vascular Malformation, Henan Provincial People's Hospital, Zhengzhou 450003, China.
Department of Hemangioma and Vascular Malformation, Henan Provincial People's Hospital, Zhengzhou 450003, China.
出版信息
Life Sci. 2019 Apr 15;223:22-28. doi: 10.1016/j.lfs.2019.03.006. Epub 2019 Mar 6.
AIMS
Infantile hemangioma (IH) is one of the most common benign vascular tumors occurred in infants. Linc00152 is a kind of long non-coding RNAs (lncRNAs) and acts as a tumor oncogene. Recent study reported that Linc00152 is highly expressed in clinical IH tissues. However, the exact biological roles have not yet been investigated. The aim of the present study was to investigate the oncogenic roles of Linc00152 in IH and the underlying mechanism in vitro.
MAIN METHODS
The expressions of Linc00152 in IH tissues and hemangioma-derived endothelial cells (HemECs) were determined using quantitative real time-PCR (qRT-PCR) analysis. The expressions of Akt/mTOR and Notch1 pathways related proteins were detected using western blot analysis. Cell proliferation was assessed by detecting Ki67 expression and CCK-8 assay. Cell apoptosis was evaluated by detecting apoptotic rate, caspase-3/7 activity, and Bcl-2 and Bax expression.
KEY FINDINGS
The results demonstrated Linc00152 was up-regulated in clinical IH tissues and HemECs. Knockdown of Linc00152 in HemECs suppressed the activation of Akt/mTOR and Notch1 signaling pathways and caused reduction in cell proliferation and Ki67 expression in HemECs. Besides, Linc00152 knockdown resulted in a significant increase in apoptotic rate, caspase-3/7 activity, and Bax expression level, as well as a decrease in Bcl-2 expression level. However, the effects of Linc00152 knockdown on cell proliferation and apoptosis were mitigated by overexpression of Akt or Notch1.
SIGNIFICANCE
Knockdown of Linc00152 suppressed HemECs proliferation and induced apoptosis via inhibiting Akt/mTOR and Notch1 signaling pathways.
目的
婴儿血管瘤（IH）是婴儿中最常见的良性血管肿瘤之一。Linc00152 是一种长链非编码 RNA（lncRNA），作为肿瘤癌基因发挥作用。最近的研究报道，Linc00152 在临床 IH 组织中高度表达。然而，其确切的生物学作用尚未得到研究。本研究旨在探讨 Linc00152 在 IH 中的致癌作用及其在体外的潜在机制。
主要方法
采用实时定量 PCR（qRT-PCR）分析检测 IH 组织和血管内皮细胞（HemECs）中 Linc00152 的表达。采用 Western blot 分析检测 Akt/mTOR 和 Notch1 通路相关蛋白的表达。通过检测 Ki67 表达和 CCK-8 测定评估细胞增殖。通过检测细胞凋亡率、caspase-3/7 活性以及 Bcl-2 和 Bax 表达评估细胞凋亡。
主要发现
结果表明，Linc00152 在临床 IH 组织和 HemECs 中上调。在 HemECs 中敲低 Linc00152 抑制 Akt/mTOR 和 Notch1 信号通路的激活，并导致 HemECs 增殖减少和 Ki67 表达降低。此外，Linc00152 敲低导致凋亡率、caspase-3/7 活性和 Bax 表达水平显著增加，Bcl-2 表达水平降低。然而，Linc00152 敲低对细胞增殖和凋亡的影响可被 Akt 或 Notch1 的过表达减轻。
意义
敲低 Linc00152 通过抑制 Akt/mTOR 和 Notch1 信号通路抑制 HemECs 增殖并诱导凋亡。
Zotero 插件