CAS Key Laboratory of Experimental Marine Biology, CAS Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, China.
Int J Mol Sci. 2020 Oct 19;21(20):7725. doi: 10.3390/ijms21207725.
MicroRNAs (miRNAs) are small non-coding RNAs with important roles in diverse biological processes including immunity. Japanese flounder () is an aquaculture fish species susceptible to the infection of bacterial and viral pathogens including . In a previous study, pol-miR-novel_547, a novel miRNA of flounder with unknown function, was found to be induced by . In the present study, we investigated the regulation and function of pol-miR-novel_547 and its target gene. We found that pol-miR-novel_547 was regulated differently by and the viral pathogen megalocytivirus, and pol-miR-novel_547 repressed the expression of PTEN (phosphatase and tensin homolog) of flounder (PoPTEN). PoPTEN is ubiquitously expressed in multiple tissues of flounder and responded to bacterial and viral infections. Interference with PoPTEN expression in flounder cells directly or via pol-miR-novel_547 promoted invasion. Consistently, in vivo knockdown of PoPTEN enhanced dissemination in flounder tissues, whereas in vivo overexpression of PoPTEN attenuated dissemination but facilitated megalocytivirus replication. Further in vitro and in vivo studies showed that PoPTEN affected autophagy activation via the AKT/mTOR pathway and also modulated the process of apoptosis. Together these results reveal for the first time a critical role of fish PTEN and its regulatory miRNA in pathogen infection, autophagy, and apoptosis.
微小 RNA（miRNAs）是一类在包括免疫在内的多种生物学过程中具有重要作用的小非编码 RNA。牙鲆（ ）是一种水产养殖鱼类，易受到细菌和病毒病原体的感染，包括 。在之前的研究中，发现了一种新的牙鲆 miRNA pol-miR-novel_547，其功能未知，该 miRNA 可被 诱导。在本研究中，我们研究了 pol-miR-novel_547 及其靶基因的调控和功能。我们发现，pol-miR-novel_547 被 和病毒病原体淋巴囊肿病毒以不同的方式调控，pol-miR-novel_547 抑制牙鲆的 PTEN（磷酸酶和张力蛋白同源物）表达（PoPTEN）。PoPTEN 在牙鲆的多种组织中广泛表达，并对细菌和病毒感染产生反应。直接或通过 pol-miR-novel_547 干扰牙鲆细胞中的 PoPTEN 表达会促进 的入侵。一致地，体内敲低 PoPTEN 会增强 在牙鲆组织中的传播，而体内过表达 PoPTEN 会促进 传播，但会阻碍淋巴囊肿病毒的复制。进一步的体外和体内研究表明，PoPTEN 通过 AKT/mTOR 通路影响自噬的激活，也调节细胞凋亡的过程。这些结果首次揭示了鱼类 PTEN 及其调控 miRNA 在病原体感染、自噬和细胞凋亡中的关键作用。
