LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins  

作　　者：Lingling Wang Xiaojuan Fang Ziyou Yang Xueling Li Mengdi Cheng Liang Cheng Ganglin Wang Wei Li Lin Liu 

机构地区：[1]Key Laboratory of Laboratory Medicine,Ministry of Education of China,Zhejiang Provincial Key Laboratory of Medical Genetics,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China [2]Zhuji Affiliated Hospital of Wenzhou Medical University,Shaoxing 311800,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第10期1606-1617,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(No.81970753);the Wenzhou Science and Technology Bureau Foundation(No.ZY2021011).

摘　　要：Long noncoding RNAs(lncRNAs)have been widely proven to be involved in liver lipid homeostasis.Herein,we identify an upregulated lncRNA named lncRP11-675F6.3 in response to rapamycin treatment using a microarray in HepG2 cells.Knockdown of lncRP11-675F6.3 leads to a significant reduction in apolipoprotein 100(ApoB100),microsomal triglyceride transfer protein(MTTP),ApoE and ApoC3 with increased cellular triglyceride level and autophagy.Furthermore,we find that ApoB100 is obviously colocalized with GFP-LC3 in autophagosomes when lncRP11-675F6.3 is knocked down,indicating that elevated triglyceride accumulation likely related to autophagy induces the degradation of ApoB100 and impairs very low-density lipoprotein(VLDL)assembly.We then identify and validate that hexokinase 1(HK1)acts as the binding protein of lncRP11-675F6.3 and mediates triglyceride regulation and cell autophagy.More importantly,we find that lncRP11-675F6.3 and HK1 attenuate high fat diet induced nonalcoholic fatty liver disease(NAFLD)by regulating VLDL-related proteins and autophagy.In conclusion,this study reveals that lncRP11-675F6.3 is potentially involved in the downstream of mTOR signaling pathway and the regulatory network of hepatic triglyceride metabolism in cooperation with its interacting protein HK1,which may provide a new target for fatty liver disorder treatment.

关 键 词：lncRP11-675F6.3 TRIGLYCERIDES AUTOPHAGY LIPOPROTEIN hexokinase 1 nonalcoholic fatty liver disease 

分 类 号：R735.7[医药卫生—肿瘤]