MiR-98 Promotes Apoptosis of Glioma Cells via Suppressing IKBKE/NF-κB Pathway.

MiR-98 Promotes Apoptosis of Glioma Cells via Suppressing IKBKE/NF-κB Pathway.
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MiR-98 通过抑制 IKBKE/NF-kappaB 途径促进胶质瘤细胞凋亡。

DOI:
10.1177/1533034617745761
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发表时间:
2017-12
影响因子:
2.8
通讯作者:
Zhang H
Zhang H
中科院分区:
医学4区
文献类型:
--
作者:
Wang L;Guo S;Zhang H

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kappa B激酶抑制剂在胶质瘤中过表达,通过激活核因子-kappa B发挥抗凋亡作用。microRNA-98可抑制胶质瘤,调节核因子-kappa B的活性,并与kappa B激酶抑制剂mRNA的3′非翻译区结合。本研究旨在探讨microRNA-98对脑胶质瘤中kappa B激酶抑制因子β 1/核因子-kappa B的调节作用。结果表明microRNA-98在胶质瘤细胞系和人脑胶质瘤组织中表达下调。microRNA-98在U87 MG和T98 G胶质瘤细胞中的过表达显著增加了紫外线诱导的胶质瘤细胞凋亡,并抑制了胶质瘤细胞核因子-κ B荧光素酶活性、核因子-κ B p50亚基表达和B细胞淋巴瘤-2(Bcl-2)表达。沉默kappa B激酶抑制剂可降低核因子-kappa B p50亚基的表达和核因子-kappa B荧光素酶活性,而表达kappa B激酶抑制剂后,核因子-kappa B活性可显著恢复。这些结果表明,microRNA-98可通过抑制kappa B激酶抑制剂β 1/核因子-kappa B信号通路促进胶质瘤细胞凋亡,并通过直接抑制kappa B激酶抑制剂β 1/核因子-kappa B表达,提示microRNA-98可能是一条新的调控途径。
The inhibitor of kappa B kinase epsilon is overexpressed in glioma and plays antiapoptotic role via activating nuclear factor-kappa B. microRNA-98 can suppress glioma, modulate the activities of nuclear factor-kappa B, and bind to the 3′-untranslated region of inhibitor of kappa B kinase epsilon messenger RNA. This study was aimed to investigate the modulation of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B by microRNA-98 in glioma. The results indicated that microRNA-98 was downregulated in glioma cell lines and human glioma tissues. Overexpression of microRNA-98 in U87MG and T98G glioma cells significantly increased the apoptosis induced by ultraviolet irradiation and suppressed nuclear factor-kappa B luciferase activity, nuclear factor-kappa B p50 subunit expression, and B-cell lymphoma-2 (Bcl-2) expression in glioma cells. Silencing inhibitor of kappa B kinase epsilon decreased the expression of nuclear factor-kappa B p50 subunit and the luciferase activity of nuclear factor-kappa B, while the nuclear factor-kappa B activity could be significantly retrieved when inhibitor of kappa B kinase epsilon was expressed in microRNA-98-transfected cells. These findings indicated that microRNA-98 could promote apoptosis of glioma cells via inhibiting inhibitor of kappa B kinase epsilon/nuclear factor-kappa B signaling and presented a novel regulatory pathway of microRNA-98 by direct suppression of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B expression in glioma cells.
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