gga-miR-181a 调节 ANP32A 表达并抑制 MDCC-MSB-1 细胞。

Gga-miR-181a modulates ANP32A expression and inhibits MDCC-MSB-1 cell.

机构信息

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

College of Animal Science and Veterinary Medicine, Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, Tianjin Agricultural University, Tianjin, 300384, China.

出版信息

In Vitro Cell Dev Biol Anim. 2021 Mar;57(3):272-279. doi: 10.1007/s11626-021-00550-0. Epub 2021 Mar 8.

DOI:10.1007/s11626-021-00550-0

PMID:33686586

Abstract

Marek's disease (MD), a highly contagious T cell lymphoid neoplasia disease of chickens, causes huge economic losses to the poultry industry. It is the only one tumor disease which can be prevented by vaccine in chickens; therefore, MD is considered to be an excellent model to study the pathogenesis of virus-induced cancer. Recently, abundant evidences have verified that miRNAs are regulators in the process of neoplastic transformation. In our previous study on miRNome analysis of MDV-induced lymphoma in chicken, we found that gga-miR-181a was downregulated drastically in MDV-infected spleens. To further investigate the role of gga-miR-181a in MDV-induced lymphomagenesis, we performed cell migration assay, and the results suggested that gga-miR-181a suppressed the migration of MDV-transformed lymphoid cell (MSB-1). Subsequently, luciferase reporter gene assay revealed that acidic nuclear phosphoprotein 32A (ANP32A) was a functional target gene of gga-miR181a. Real-time PCR and western blot assay showed that the mRNA and protein levels of ANP32A were downregulated in gga-miR-181a mimic group at 48-h and 96-h post-transfection, respectively, indicating that ANP32A was modulated by gga-miR-181a. All the results suggested that gga-miR-181a was an inhibitor in MSB-1 cell migration. ANP32A was a direct target gene of gga-miR-181a and they were implicated in MD lymphoma tumorigenesis.

摘要

马立克氏病（MD）是一种高度传染性的鸡 T 细胞淋巴肿瘤性疾病，给家禽业造成巨大的经济损失。它是唯一一种可以通过疫苗预防的鸡肿瘤病，因此 MD 被认为是研究病毒诱导癌症发病机制的理想模型。最近，大量证据证实 miRNA 是肿瘤转化过程中的调节因子。在我们之前关于 MDV 诱导鸡淋巴瘤的 miRNome 分析研究中，发现 gga-miR-181a 在 MDV 感染的脾脏中明显下调。为了进一步研究 gga-miR-181a 在 MDV 诱导的淋巴肿瘤发生中的作用，我们进行了细胞迁移实验，结果表明 gga-miR-181a 抑制了 MDV 转化的淋巴样细胞（MSB-1）的迁移。随后，荧光素酶报告基因实验显示酸性核磷蛋白 32A（ANP32A）是 gga-miR181a 的功能靶基因。实时 PCR 和 Western blot 实验显示，在转染后 48 小时和 96 小时，gga-miR-181a 模拟物组的 ANP32A 的 mRNA 和蛋白水平分别下调，表明 ANP32A 受 gga-miR-181a 调节。所有结果表明，gga-miR-181a 是 MSB-1 细胞迁移的抑制剂。ANP32A 是 gga-miR-181a 的直接靶基因，它们参与 MD 淋巴瘤的肿瘤发生。