miRNAs介导禽J亚群白血病病毒多潜能致瘤的分子机制

Avian leukosis virus subgroup J (ALV-J) has multiple potential tumorigenic characteristics. Different ALV-J strains induce diverse tumor types via changing microenvironments of host cells. However, the molecular mechanism of its multiple potential tumorigenic characteristics remains unclear. Our previous studies found there was a very close relationship between the changes of miRNAs expressions and multiple potential tumorigenic characteristics of ALV-J. To reveal the molecular mechanism by which miRNAs regulate multiple potential tumorigenic characteristics of ALV-J, this study focuses on the most frequently occurring tumors of ALV-J, screens the specific miRNAs via molecular biological technique, identifies which viral elements regulate the corresponding miRNAs, and explores the key molecules in the viral element-miRNA-target protein-tumor pathway. The discovery of the miRNA-mediated the ALV-J multi-potential tumorigenic signal pathway network provides a new research idea and lays a scientific foundation for the study on the mechanism of the retroviral multi-potential tumorigenic characteristics, providing theoretical guidance for the prevention and control of ALV-J.

禽J亚群白血病病毒（ALV-J）具有多潜能致瘤特性，不同ALV-J毒株通过改变宿主细胞的微环境诱导不同的肿瘤型，但其分子机制尚不明晰。我们在对ALV-J致瘤多样性的研究中捕捉到了miRNA表达量变化与ALV-J多潜能致瘤的密切关系，为揭示miRNA调控ALV-J致瘤多样性的分子机制，本研究聚焦于临床中频发高发的ALV-J肿瘤型，利用分子生物学前沿技术，筛选鉴定ALV-J肿瘤型密切相关的特异miRNA，确定对miRNA起调控作用的病毒元件，明确病毒元件-miRNA-靶标蛋白-肿瘤通路中关键分子，揭示miRNA对ALV-J多潜能致瘤的调控途径，绘制完整的miRNAs介导ALV-J多潜能致瘤的信号通路网络图，为阐明ALV-J多潜能致瘤分子机制提供全新的研究思路，为反转录病毒多潜能致瘤机制的研究提供科学基础，同时也为ALV-J的防控提供理论指导。

基于ALV-J诱导多种恶性肿瘤对养禽业的严重危害，阐明miRNAs介导的ALV-J致瘤多样性分子机制对于防控ALV-J感染具有重要的现实意义。本研究聚焦于临床中频发高发的ALV-J肿瘤型，以髓细胞瘤、血管瘤及纤维肉瘤为研究对象，通过筛选不同肿瘤型特异miRNA，鉴定调控miRNA的病毒结构元件及致瘤信号通路，成功发现了2个对ALV-J诱导血管瘤起关键调控作用的miRNA（miR-23b-3p和miR-147），明确了gag元件对miR-23b-3p和miR-147表达抑制的决定作用，鉴定了3个与血管瘤形成密切相关的miRNA靶标分子（KIAA1199、NF-κB p50和CCND1），揭示了ALV-J gag-miR-23b-3p-CCND1-细胞周期G1/S期转变-细胞增殖通路及ALV-J gag-MSI1-miR-147-NF-κB/KIAA1199/EGFR-血管瘤形成通路，从miRNA角度阐明了ALV-J诱导血管瘤分子机制，为进一步挖掘ALV-J多潜能致瘤机制奠定科学基础。