Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis,FEBS Open Bio

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Intracellular microRNA expression patterns influence cell death fates for both necrosis and apoptosis
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-10-06 , DOI: 10.1002/2211-5463.12995
Akira Sato ₁ , Akihiro Yamamoto ₂ , Akira Shimotsuma ₁ , Yoko Ogino _{1,

3} , Naoki Funayama ₁ , Yui Takahashi ₁ , Akiko Hiramoto ₂ , Yusuke Wataya ₂ , Hye-Sook Kim ₂

Affiliation

MicroRNAs (miRNAs) are small noncoding RNA molecules that interact with target mRNAs at specific sites to induce cleavage of the mRNA or inhibit translation. Such miRNAs play a vital role in gene expression and in several other biological processes, including cell death. We have studied the mechanisms regulating cell death (necrosis in original F28‐7 cells and apoptosis in their variant F28‐7‐A cells) in the mouse mammary tumor cell line FM3A using the anticancer agent floxuridine (FUdR). We previously reported that inhibition of heat‐shock protein 90 by the specific inhibitor geldanamycin (GA) in F28‐7 cells causes a shift from necrosis to apoptosis. In this study, we investigated the intracellular miRNA expression profiles of FUdR‐treated F28‐7 cells (necrotic condition), GA plus FUdR‐treated F28‐7 cells (apoptotic condition), and FUdR‐treated F28‐7‐A cells (apoptotic condition) through miRNA microarray analysis. In addition, we knocked down Dicer, a key molecule for the expression of mature miRNAs, in F28‐7 cells to examine whether it modulates FUdR‐induced cell death. Our analysis revealed that the miRNA expression patterns differ significantly between these cell death conditions. Furthermore, we identified miRNA candidates that regulate cell death. Knockdown of Dicer in FUdR‐treated necrosis‐fated cells caused a partial shift from necrosis to apoptosis. These findings suggest that modulation of miRNA expression patterns influences the decision of cell death fate toward necrosis or apoptosis. Our findings may serve as a basis for further study of the functions of miRNAs in cell death mechanisms.

中文翻译：

细胞内 microRNA 表达模式影响坏死和凋亡的细胞死亡命运

MicroRNA (miRNA) 是小的非编码 RNA 分子，它们在特定位点与靶 mRNA 相互作用以诱导 mRNA 的切割或抑制翻译。此类 miRNA 在基因表达和其他几个生物学过程（包括细胞死亡）中起着至关重要的作用。我们研究了使用抗癌剂氟尿苷 (FUdR) 在小鼠乳腺肿瘤细胞系 FM3A 中调节细胞死亡（原始 F28-7 细胞坏死和变异 F28-7-A 细胞凋亡）的机制。我们之前报道过，特异性抑制剂格尔德霉素 (GA) 在 F28-7 细胞中对热休克蛋白 90 的抑制会导致细胞从坏死转变为凋亡。在这项研究中，我们研究了 FUdR 处理的 F28-7 细胞（坏死条件）、GA 加 FUdR 处理的 F28-7 细胞（凋亡条件）的细胞内 miRNA 表达谱，和 FUdR 处理的 F28-7-A 细胞（凋亡条件）通过 miRNA 微阵列分析。另外，我们打倒了Dicer是 F28-7 细胞中成熟 miRNA 表达的关键分子，以检查它是否调节 FUdR 诱导的细胞死亡。我们的分析表明，这些细胞死亡条件之间的 miRNA 表达模式存在显着差异。此外，我们确定了调节细胞死亡的 miRNA 候选者。在 FUdR 处理的坏死命运细胞中敲除Dicer导致部分从坏死转变为凋亡。这些发现表明，miRNA 表达模式的调节影响细胞死亡命运对坏死或凋亡的决定。我们的研究结果可作为进一步研究 miRNA 在细胞死亡机制中的功能的基础。

更新日期：2020-11-04

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