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靶向PDPK1的gga-miR-148a-5p抑制禽白血病病毒J亚群（ALV-J）感染细胞的增殖和细胞周期进程。

gga-miR-148a-5p-Targeting PDPK1 Inhibits Proliferation and Cell Cycle Progression of Avain Leukosis Virus Subgroup J (ALV-J)-Infected Cells.

作者信息

Yu Heling, Xu Hengyong, Yan Chaoyang, Zhu Shiliang, Lan Xi, Lu Yuxiang, He Qijian, Yin Huadong, Zhu Qing, Zhao Xiaoling, Li Diyan, Liu Yiping, Wang Yan

机构信息

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

College of Animal Science and Technology, Southwest University, Chongqing, China.

出版信息

Front Cell Dev Biol. 2020 Dec 15;8:587889. doi: 10.3389/fcell.2020.587889. eCollection 2020.

DOI:10.3389/fcell.2020.587889
PMID:33384993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7769946/
Abstract

Avian leukosis virus subgroup J disease (ALV-J) is a contagious and immunosuppressive avian disease caused by ALV-J virus. Although miRNA participate in various biological processes of tumors, little is known about the potential role of miRNA in ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of gga-miR-148a-5p was significantly different in ALV-J-infected chicken spleens compared with non-infected chickens. The aim of this study was to investigate the functional roles of gga-miR-148a-5p and identify downstream targets regulated by gga-miR-148a-5p in ALV-J-infected chickens. We found that the expression of gga-miR-148a-5p was significantly downregulated during ALV-J infection of chicken embryo fibroblasts (CEF). Dual luciferase reporter assays demonstrated that PDPK1 is a direct target gene of gga-miR-148a-5p. , overexpression of gga-miR-148a-5p significantly promoted ALV-J-infected CEF cell proliferation, included cell cycle, whereas inhibition of gga-miR-148a-5p had an opposite effect. Inhibition of PDPK1 promoted the proliferation of ALV-J-infected cells but had no effect on the activity of NF-κB. Together, these results suggested that gga-miR-148a-5p targets PDPK1 to inhibit the proliferation and cell cycle of ALV-J-infected CEF cells. Our study provides a new understanding for the tumor mechanism of ALV-J infection.

摘要

J亚群禽白血病病毒病（ALV-J）是由ALV-J病毒引起的一种具有传染性和免疫抑制性的禽类疾病。尽管微小RNA（miRNA）参与肿瘤的各种生物学过程，但关于miRNA在ALV-J中的潜在作用却知之甚少。我们之前的miRNA和RNA测序数据表明，与未感染的鸡相比，gga-miR-148a-5p在感染ALV-J的鸡脾脏中的表达存在显著差异。本研究的目的是探讨gga-miR-148a-5p的功能作用，并鉴定其在感染ALV-J的鸡中调控的下游靶标。我们发现，在鸡胚成纤维细胞（CEF）感染ALV-J的过程中，gga-miR-148a-5p的表达显著下调。双荧光素酶报告基因检测表明，PDPK1是gga-miR-148a-5p的直接靶基因。过表达gga-miR-148a-5p显著促进了感染ALV-J的CEF细胞增殖，包括细胞周期，而抑制gga-miR-148a-5p则产生相反的效果。抑制PDPK1促进了感染ALV-J的细胞增殖，但对NF-κB的活性没有影响。总之，这些结果表明，gga-miR-148a-5p靶向PDPK1以抑制感染ALV-J的CEF细胞的增殖和细胞周期。我们的研究为ALV-J感染的肿瘤机制提供了新的认识。

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