Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.
Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway.
复制标题
西达本胺通过 MEK/ERK 信号通路下调 lncRNA VPS9D1-AS1 抑制急性髓系白血病细胞增殖。
DOI：
10.3389/fphar.2020.569651
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发表时间：
2020
影响因子：
5.6
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Lin L;Que Y;Lu P;Li H;Xiao M;Zhu X;Li D
不规则的组蛋白修饰和lncRNA的异常表达与包括急性髓细胞白血病（AML）在内的多种肿瘤的发生密切相关。然而，组蛋白去乙酰化酶抑制剂对AML细胞中lncRNA表达的影响和具体的潜在分子机制尚不清楚。在这里，我们报道了一种新的组蛋白去乙酰化酶抑制剂Chidamide对AML细胞增殖和lncRNA表达的影响。西达胺抑制AML细胞增殖，阻断G1/S期转换，并通过caspase依赖的凋亡途径诱导细胞凋亡。西达胺还抑制皮下肿瘤的形成。转录组测序结果显示，西达胺处理SKM-1细胞和THP-1细胞后，1,195个lncRNA共上调，780个lncRNA共下调。结合转录组测序数据和基因表达谱交互分析数据集，我们发现VPS 9D 1-AS 1表达与AML患者的生存率呈负相关。VPS 9D 1-AS 1基因敲低可抑制细胞增殖，阻滞细胞周期，并抑制体内皮下肿瘤的形成。VPS 9D 1-AS 1过表达则有相反的作用。此外，VPS 9D 1-AS 1基因敲低可抑制MEK/ERK信号通路，从而增强Chidamide对AML细胞增殖的抑制作用。这些结果表明，VPS 9D 1-AS 1的靶向调控可能会克服Chidamide治疗AML的局限性。
Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the effects of a novel histone deacetylase inhibitor Chidamide on proliferation and lncRNA expression in AML cells. Chidamide inhibited cell proliferation, blocked G1/S phase transition, and induced cell apoptosis through the caspase-dependent apoptotic pathway in AML cells. Chidamide also inhibited the formation of subcutaneous tumors. Transcriptome sequencing results showed that 1,195 lncRNAs were co-upregulated and 780 lncRNAs were co-downregulated after Chidamide treatment of SKM-1 cells and THP-1 cells. Combined with transcriptome sequencing data and the gene expression profiling interactive analysis dataset, we found that VPS9D1-AS1 expression was negatively correlated with the survival of AML patients. VPS9D1-AS1 knockdown inhibited cell proliferation, arrested cell cycle, as well as inhibited the formation of subcutaneous tumors in vivo. VPS9D1-AS1 overexpression had the reverse effect. Furthermore, VPS9D1-AS1 knockdown inhibited the MEK/ERK signaling pathway, and thus enhanced the inhibitory effect of Chidamide on AML cell proliferation. These findings suggested that targeted regulation of VPS9D1-AS1 might overcome the limitations of Chidamide in the treatment of AML.
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影响因子：
10.1
作者：
Papaioannou D;Nicolet D;Volinia S;Mrózek K;Yan P;Bundschuh R;Carroll AJ;Kohlschmidt J;Blum W;Powell BL;Uy GL;Kolitz JE;Wang ES;Eisfeld AK;Orwick SJ;Lucas DM;Caligiuri MA;Stone RM;Byrd JC;Garzon R;Bloomfield CD
通讯作者：
Bloomfield CD
影响因子：
4.8
作者：
Lents, NH;Keenan, SM;Baldassare, JJ
通讯作者：
Baldassare, JJ
影响因子：
5.4
作者：
Li Y;Seto E
通讯作者：
Seto E
影响因子：
11.4
作者：
Beck, D.;Thoms, J. A. I.;Pimanda, J. E.
通讯作者：
Pimanda, J. E.
WT1-MEG3 信号传导功能障碍通过 p53 依赖性和非依赖性途径促进 AML 白血病发生
影响因子：
11.4
作者：
Lyu Y;Lou J;Yang Y;Feng J;Hao Y;Huang S;Yin L;Xu J;Huang D;Ma B;Zou D;Wang Y;Zhang Y;Zhang B;Chen P;Yu K;Lam EW;Wang X;Liu Q;Yan J;Jin B
通讯作者：
Jin B