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HMMR alleviates endoplasmic reticulum stress by promoting autophagolysosomal activity during endoplasmic reticulum stress-driven hepatocellular carcinoma progression

引用

Cancer Communications 2023年第9期43卷 981-1002页

作者： Lin He Hao Li Can Li Ze-Kun Liu Meng Lu Ren-Yu Zhang Dong Wu Ding Wei Jie Shao Man Liu Hao-Lin Wei Cong Zhang Zhe Wang Ling-Min Kong Zhi-Nan Chen Huijie Bian National Translational Science Centre for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxiP. R. China Department of Gastroenterology the General Hospital of Western Theatre CommandChengduSichuanP. R. China State Key Laboratory of Cancer Biology Department of PathologyXijing Hospital and School of Basic MedicineFourth Military Medical UniversityXi'anShaanxiP. R. China

Background The mechanism of hepatitis B virus(HBV)-induced carcinogenesis remains an area of *** accumulation of hepatitis B surface antigen in the endoplasmic reticulum(ER)of hepatocytes stimulates persistent ER *** of the unfolded protein response(UPR)pathway of ER stress may play an important role in inflammatory cancer *** the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma(HCC)is still ***,we aimed to define the key molecule hyaluronan-mediated motility receptor(HMMR)in this process and explore its role under ER stress in HCC *** An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor *** and transcriptomics analyses were performed to identify the potential key molecule,screen the E3 ligase,and define the activation *** real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell *** reporter assay,chromatin immunoprecipitation,coimmunoprecipitation,immunoprecipitation,and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER *** was used to clarify the expression patterns of HMMR and related molecules in human *** We found sustained activation of ER stress in the HBV-transgenic mouse model of *** was transcribed by c/EBP homologous protein(CHOP)and degraded by tripartite motif containing 29(TRIM29)after ubiquitination under ER stress,which caused the inconsistent expression of mRNA and *** expression of TRIM29 in the HCC progression regulated the dynamic expression of *** could alleviate ER stress by increasing autophagic lysosome *** negative correlation between HMMR and ER stress,positive correlation between HMMR and autophagy,and negative correlation between ER stress and

关键词： autophagy endoplasmic reticulum stress hepatitis B virus hepatocellular carcinoma HMMR TRIM29 ubiquitination and proteasomal degradation

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