HSV-2-encoded miRNA-H4 Regulates Cell Cycle Progression and Act-D-induced Apoptosis in HeLa Cells by Targeting CDKL2 and CDKN2A

HSV-2-encoded miRNA-H4 Regulates Cell Cycle Progression and Act-D-induced Apoptosis in HeLa Cells by Targeting CDKL2 and CDKN2A
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HSV-2 编码的 miRNA-H4 通过靶向 CDKL2 和 CDKN2A 调节 HeLa 细胞的细胞周期进程和 Act-D 诱导的细胞凋亡

DOI:
10.1007/s12250-019-00101-8
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发表时间:
2019-04
期刊:
影响因子:
5.5
通讯作者:
杨慧兰
杨慧兰
中科院分区:
医学2区
文献类型:
--
作者:
赵阳;杨晶晶;刘岩;樊建勇;杨慧兰

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由潜伏期相关的转录本编码的microRNA(miRNA)与单纯疱疹病毒2(HSV-2)感染的潜在和急性阶段有关。在这项研究中,MiRNA-H4-5p和miRNA-H4-3P在HeLa细胞中以异位表达以探索有效
MicroRNAs (miRNAs) encoded by latency-associated transcript are associated with both latent and acute stages of herpes simplex virus 2 (HSV-2) infection. In this study, miRNA-H4-5p and miRNA-H4-3p were ectopically expressed in HeLa cells to explore potential cellular targets of viral miRNAs and demonstrate their potential biological functions. The results showed that miRNA-H4-5p could reverse apoptosis induced by actinomycin D (Act-D) and promote cell cycle progression, but miRNA-H4-3p had no such obvious functions. Bioinformatics analysis, luciferase report assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blotting demonstrated that miRNA-H4-5p could bind to the 3′-untranslated region (UTR) of cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase-like 2 (CDKL2) to negatively regulate their expression. We verified that these two targeted genes were associated with cell apoptosis and cell cycle. Furthermore, in HeLa cells infected with HSV-2, we detected significantly reduced expression of CDKN2A and CDKL2 and demonstrated the negative regulation effect of miRNA-H4-5p on these two target genes. Our findings show that viral miRNAs play a vital role in regulating the expression of the host’s cellular genes that participate in cell apoptosis and progression to reshape the cellular environment in response to HSV-2 infection, providing further information on the roles of encoded herpesvirus miRNAs in pathogen–host interaction.
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