MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells.

MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing's sarcoma cells.
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DOI:
10.1186/s12935-018-0536-9
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发表时间:
2018
影响因子:
5.8
通讯作者:
Tsumura H
Tsumura H
中科院分区:
医学2区
文献类型:
--
作者:
Kawano M;Tanaka K;Itonaga I;Iwasaki T;Tsumura H

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microRNAs(miRNAs)是一类内源性的非编码小分子RNA,在多种生物学过程中发挥重要作用。在这里,我们表明,miRNA在尤因肉瘤(ES)细胞中FAS表达的下调中起着重要的作用。为了识别和表征ES中可能的致癌因子,我们采用基于微阵列的方法来分析5种ES细胞系和人间充质干细胞(hMSCs)中miRNA及其靶mRNA表达的变化。与hMSC相比,在所有测试的ES细胞中,miRNA,miR-181 c显著上调,而FAS受体表达显著下调。将抗miR-181 c导入ES细胞系导致FAS 2表达增加。此外,抗miR-181 c抑制ES细胞中的细胞生长和细胞周期进展。抗miR-181 c还促进ES细胞的凋亡。此外,ES细胞中miR-181 c的下调显著抑制了体内肿瘤生长。这些结果表明,miR-181 c的表达不受调节可能通过靶向FAS而促进ES。miR 181 c的减少增加FAS的表达。这证明细胞周期进程的延迟消除了凋亡抗性,从而抑制了尤文肉瘤的生长。由于FAS信号参与了细胞凋亡和肿瘤增殖的调节,我们的研究结果可能有助于ES的新的治疗靶点。
MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in multiple biological processes. Here, we show that miRNAs play an important function in the down-regulation of FAS expression in Ewing’s sarcoma (ES) cells. To identify and characterize possible oncogenic factors in ES, we employed a microarray-based approach to profile the changes in the expression of miRNAs and their target mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs). MiRNA, miR-181c, was significantly up-regulated, whereas FAS receptor expression was significantly down-regulated in all tested ES cells compared with hMSCs. Introducing anti-miR-181c into ES cell lines resulted in an increased expression of FAS2. Additionally, anti-miR-181c prohibited cell growth and cell cycle progression in ES cells. Anti-miR-181c also promoted apoptosis in ES cells. Furthermore, the down-regulation of miR-181c in ES cells significantly suppressed tumor growth in vivo. These results suggest that unregulated expression of miR-181c could contribute to ES by targeting FAS. Reduction of miR181c increased expression of FAS. This proves that retardation of cell cycle progression removes apoptosis resistance, thereby repressing the growth of Ewing sarcoma. Since FAS signaling is involved in regulation of apoptosis and tumor proliferation, our findings might contribute to new therapeutic targets for ES.
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