LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation  

作　　者：Xi Zhang Yuanyuan Li Chen Huan Yubao Hou Rujia Liu Hongyun Shi Peng Zhang Baisong Zheng Yingchao Wang Hong Wang Wenyan Zhang 

机构地区：[1]Institute of Virology and AIDS Research,The First Hospital of Jilin University,Changchun,130012,China [2]Department of Ophthalmology,The First Hospital of Jilin University,Changchun,130012,China [3]Hepatobiliary Pancreatic Surgery,The First Hospital of Jilin University,Changchun,130012,China

出　　处：《Virologica Sinica》2024年第1期44-55,共12页中国病毒学（英文版）

基　　金：supported in part by funding from the National Key R&D Program of China(2021YFC2301900,2021YFC2301903,and 2021YFC2301904);National Natural Science Foundation of China(81672004 and 81930062 to WZ;81801993 to HW);Science and Technology Department of Jilin Province(20190101003JH,20190201272JC,20200201331JC,and 20200201422JC);the Key Laboratory of Molecular Virology,Jilin Province(20102209);supported by Fundamental Research Funds for Central Universities.

摘　　要：Hepatitis B virus(HBV)infection results in liver cirrhosis and hepatocellular carcinoma(HCC).HBx/nuclear factor(NF)-κB pathway plays a role in HBV replication.However,whether NF-κB-interacting long noncoding RNA(NKILA),a suppressor of NF-κB activation,regulates HBV replication remains largely unknown.In this study,gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB activity.In turn,HBV infection down-regulated NKILA expression.In addition,expression levels of NKILA were lower in the peripheral blood-derived monocytes(PBMCs)of HBV-positive patients than in healthy individuals,which were correlated with HBV viral loads.And a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive patients.Lower levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome,HBV-infected HepG2-NTCP cells,stable HBV-producing HepG2.2.15 and HepAD38 cells,compared to those HBV-negative cells.Furthermore,HBx was required for NKILA-mediated inhibition on HBV replication.NKILA decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65,whereas NKILA mutants lack of essential domains for NF-κB inhibition,lost the ability to inhibit HBV replication.Together,our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-κB signalling.

关 键 词：LncRNA NF-κB-interacting longnoncoding RNA(NKILA) NF-ĸB signalling ChronichepatitisBvirus(HBV) Viral replication HBX 

分 类 号：S852.4[农业科学—基础兽医学]