LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.

LncRNA-uc002mbe.2 Interacting with hnRNPA2B1 Mediates AKT Deactivation and p21 Up-Regulation Induced by Trichostatin in Liver Cancer Cells.
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LncRNA-uc002mbe.2 与 hnRNPA2B1 相互作用介导曲古抑菌素在肝癌细胞中诱导的 AKT 失活和 p21 上调

DOI:
10.3389/fphar.2017.00669
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发表时间:
2017
影响因子:
5.6
通讯作者:
Yang H
Yang H
中科院分区:
医学2区
文献类型:
--
作者:
Chen T;Gu C;Xue C;Yang T;Zhong Y;Liu S;Nie Y;Yang H

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长链非编码RNA(lncRNA)参与了肝癌的发生。我们以前发现,lncRNA-uc 002 mbe.2的诱导与肝细胞癌(HCC)细胞中的阿司他丁A(TSA)的凋亡效应呈正相关。本研究进一步分析了uc002mbe.2在TSA诱导的肝癌细胞死亡中的作用。TSA可使肝癌细胞胞浆中uc002mbe.2表达明显增加。敲低uc002mbe.2抑制TSA诱导的G2/M期细胞周期阻滞、p21诱导和Huh 7细胞凋亡,并逆转TSA介导的p-AKT降低。RNA下拉和RNA结合蛋白免疫沉淀(RIP)分析显示,TSA诱导之间的相互作用uc002mbe.2和异质核核糖核蛋白A2 B1(hnRNPA 2B 1)在Huh 7细胞。这种相互作用介导肝癌细胞中AKT失活和p21诱导。在无胸腺异种移植小鼠模型中,uc002mbe.2的敲低显著抑制了TSA介导的肿瘤大小和重量的减少。此外,TSA降低hnRNPA 2B 1和p-AKT水平并诱导异种移植肿瘤中p21的能力被uc002mbe.2敲低所阻止。因此,uc002mbe.2和hnRNPA 2B 1在介导AKT失活和p21诱导中的相互作用参与了阿司他汀在肝癌细胞中的细胞抑制作用。
Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.
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