Chen Liyi, Xu Huijuan, Liu Ruiheng, Yao Ziqi, Xie Qingmei, Zhang Xinheng
State Key Laboratory of Swine and Poultry Breeding Industry & Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, Guangzhou 510642, PR China; Zhongshan Innovation Center, South China Agricultural University, Zhongshan 528400, PR China; South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, Guangzhou 510642, PR China; Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangdong, Guangzhou 510642, PR China.
State Key Laboratory of Swine and Poultry Breeding Industry & Heyuan Branch, Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and Technology, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Engineering Research Center for Vector Vaccine of Animal Virus, Guangzhou 510642, PR China; Zhongshan Innovation Center, South China Agricultural University, Zhongshan 528400, PR China; South China Collaborative Innovation Center for Poultry Disease Control and Product Safety, Guangzhou 510642, PR China; Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangdong, Guangzhou 510642, PR China.
Poult Sci. 2025 Apr;104(4):104923. doi: 10.1016/j.psj.2025.104923. Epub 2025 Feb 17.
Avian leukosis virus subgroup J (ALV-J) is an immunosuppressive neoplastic virus, the growth retardation and growth performance of chickens after infection. Circular RNAs (circRNAs) play a crucial role in various types of cancer. In a previous study, we showed that circ-Vav3 was significantly elevated in the tumor livers of avian leukosis-infected chickens. Autophagy is an essential cellular process, and circRNAs have been confirmed to be key players in autophagy regulation. In this study, we demonstrated that overexpression of circ-Vav3 inhibited autophagy. Specifically, circ-Vav3 functions as a sponge for gga-miR-375, resulting in increased expression of CIP2A, which is a target gene of gga-miR-375. CIP2A, in turn, hinders the fusion of autophagosomes with lysosomes, leading to incomplete autophagic flux, consequently, the inhibition of autophagy. Further study confirmed that overexpression of gga-miR-375 inhibits CIP2A expression and promotes autophagy by downregulating p-AKT. Additionally, we treated cells with rapamycin to induce autophagy and then cotransfected them with circ-Vav3 and gga-miR-375. The results demonstrated that cotransfection of circ-Vav3 and gga-miR-375 inhibited cellular autophagy. Moreover, cells cotransfected with circ-Vav3 and gga-miR-375 exhibited further autophagy inhibition after ALV-J infection, suggesting that circ-Vav3 is involved in inhibiting autophagy caused by ALV-J infection through the regulation of gga-miR-375/CIP2A/AKT. In conclusion, our results demonstrated that circ-Vav3 inhibited autophagy through the gga-miR-375/CIP2A/AKT pathway and mediated the suppression of ALV-J-induced autophagy.
禽白血病病毒J亚群（ALV-J）是一种免疫抑制性肿瘤病毒，感染后会影响鸡的生长发育和生长性能。环状RNA（circRNAs）在各类癌症中发挥着关键作用。在先前的一项研究中，我们发现circ-Vav3在感染禽白血病的鸡的肿瘤肝脏中显著上调。自噬是一种重要的细胞过程，并且circRNAs已被证实是自噬调控的关键因子。在本研究中，我们证明了circ-Vav3的过表达抑制自噬。具体而言，circ-Vav3作为gga-miR-375的海绵，导致CIP2A表达增加，CIP2A是gga-miR-375的靶基因。反过来，CIP2A阻碍自噬体与溶酶体的融合，导致自噬流不完整，从而抑制自噬。进一步的研究证实，gga-miR-375的过表达通过下调p-AKT来抑制CIP2A表达并促进自噬。此外，我们用雷帕霉素处理细胞以诱导自噬，然后将circ-Vav3和gga-miR-375共转染到细胞中。结果表明，circ-Vav3和gga-miR-375共转染抑制细胞自噬。此外，circ-Vav3和gga-miR-375共转染的细胞在ALV-J感染后表现出进一步的自噬抑制，这表明circ-Vav3通过调节gga-miR-375/CIP2A/AKT参与抑制ALV-J感染引起的自噬。总之，我们的结果表明circ-Vav3通过gga-miR-375/CIP2A/AKT途径抑制自噬，并介导对ALV-J诱导的自噬的抑制。
