NORHA,a novel follicular atresia-related lncRNA,promotes porcine granulosa cell apoptosis via the miR-183-96-182 cluster and FoxO1 axis  

作　　者：Wang Yao Zengxiang Pan Xing Du Jinbi Zhang Honglin Liu Qifa Li 

机构地区：[1]College of Animal Science and Technology,Nanjing Agricultural University,Nanjing 210095,China

出　　处：《Journal of Animal Science and Biotechnology》2022年第2期441-457,共17页畜牧与生物技术杂志（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(32072693 and 31630072);the Qing Lan Project of Jiangsu Province(2020).

摘　　要：Background:Follicular atresia has been shown to be strongly associated with a low follicle utilization rate and female infertility,which are regulated by many factors such as microRNAs(miRNAs),which constitute a class of noncoding RNAs(ncRNAs).However,little is known about long noncoding RNAs(lncRNAs),which constitute another ncRNA family that regulate follicular atresia.Results:A total of 77 differentially expressed lncRNAs,including 67 upregulated and 10 downregulated lncRNAs,were identified in early atretic follicles compared to healthy follicles by RNA-Sequencing.We characterized a noncoding RNA that was highly expressed in atretic follicles(NORHA).As an intergenic lncRNA,NORHA was one of the upregulated lncRNAs identified in the atretic follicles.To determine NORHA function,RT-PCR,flow cytometry and western blotting were performed,and the results showed that NORHA was involved in follicular atresia by influencing GC apoptosis with or without oxidative stress.To determine the mechanism of action,bioinformatics analysis,luciferase reporter assay and RNA immunoprecipitation assay were performed,and the results showed that NORHA acted as a‘sponge’,that directly bound to the miR-183-96-182 cluster,and thus prevented its targeted inhibition of FoxO1,a major sensor and effector of oxidative stress.Conclusions:We provide a comprehensive perspective of lncRNA regulation of follicular atresia,and demonstrate that NORHA,a novel lncRNA related to follicular atresia,induces GC apoptosis by influencing the activities of the miR-183-96-182 cluster and FoxO1 axis.

关 键 词：Follicular atresia Granulosa cell apoptosis ncRNA NORHA Oxidative stress 

分 类 号：S852[农业科学—基础兽医学]