The regulatory role of endoplasmic reticulum stress-related long non-coding RNA Gm9795 in hepatocellular carcinoma
Mingming WANG
;
Weiwei SHANG
;
Guoping ZHAO
Tumor.2025;45(2):111-125. doi:10.3781/j.issn.1000-7431.2025.2309-0472
Objective:To investigate the role of endoplasmic reticulum stress(ERS)-related long non-coding RNA(lnc RNA)Gm9795 in the progression of hepatocellular carcinoma(HCC).Methods:This retrospective cohort study included 80 HCC patients who underwent routine surgical procedures at Nanjing Jiangning Hospital from 2014 to 2020.Colecting clinical datas from all patients and using real-time fluorescence quantitative PCR to detect the expression level of Gm9795 in 80 patients'cancer and adjacent tissues,as well as in HCC cells(HepG2,Hep3B,HCCLM3,and Huh7).The correlation between Gm9795 expression and overall survival time and recurrence free survival time of HCC patients was analysised.Constructing HCCLM3 cells overexpressing Gm9795 through lentiviral infection,and constructing Huh7 cells silencing Gm9795 expression through liposome transfection.The proliferation ability of cells was evaluated using CCK-8 assay and colony formation assay,while the migration and invasion ability of cells were detected using Transwell assay.Identification of Gm9795 specific binding protein by mass spectrometry(MS).The effect of overexpressing or silencing Gm9795 expression on the expression of C/EBP homologous protein(CHOP)gene was detected by Western blotting.The CHOP gene was simultaneously transferred into HCCLM3 cells overexpressing Gm9795,and the effects of up-regulating CHOP expression level on the proliferation,migration,and invasion of HCCLM3 cells were evaluated using CCK-8 assay,colony formation assay,and Transwell assay.Results:Compared with adjacent tissues,the expression level of Gm9795 was significantly up-regulated in HCC tissues(P<0.001).The expression levels of Gm9795 in all HCC cells were significantly higher than in normal hepatocytes LO2(all P<0.05).Higher expression levels of Gm9795 were associated with aggressive clinical pathological features,including tumor size,multiple tumors,Barcelona Clinic Liver Cancer(BCLC)staging,and portal vein tumor thrombus(all P<0.05).The results of multivariate analysis showed that high expression level of Gm9795 was an independent prognostic factor for overall survival and recurrence free survival in HCC patients(both P<0.05).The higher expression of Gm9795 was significantly correlated with shorter overall survival and recurrence free survival in the cohort(both P<0.01).Compared with the Vector group,the proliferation,migration,and invasion of HCCLM3 cells were significantly enhanced in the Gm9795 overexpression group(all P<0.01);Compared with the siNC group,the proliferation,migration,and invasion of Huh7 cells were significantly reduced in the siGm9795-1 and siGm9795-2 groups(all P<0.01).CHOP was identified as a Gm9795 specific binding protein by MS.Compared with the Gm9795+Vector group,the Gm9795+CHOP group showed significant reductions in proliferation,migration,and invasion of HCCLM3 cells(all P<0.01).Conclusions:Gm9795 is up-regulated in HCC tissues,and the high expression of Gm9795 is an independent prognostic factor for the overall survival of HCC patients.Gm9795 promotes the proliferation and invasion of HCC cells in vitro,and its mechanism may be related to the inhibition of ERS mediated by CHOP signaling pathway.
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