LncRNA Meg3 expression level is negatively correlated with liver fibrosis severity in patients with Wilson disease

HUA Daiping; XUAN Qiaoyu; SUN Lanting; YU Qingsheng; WANG Qin; WANG Tao; MA Qiyan; YANG Wenming; WANG Han

doi:10.12122/j.issn.1673-4254.2025.11.09

Abstract：Objective To investigate the expression of the long non-coding RNA maternally expressed gene 3(LncRNA Meg3)in patients with the Wilson disease(WD)and its correlation with the severity of liver fibrosis and autophagy-related markers.Methods A total of 100 WD patients and 50 healthy individuals were enrolled from the First Affiliated Hospital of Anhui University of Chinese Medicine.Serum biomarkers,including platelet count,hyaluronic acid(HA),laminin(LN),type III procollagen N-terminal peptide(PIIINP),type Ⅳ collagen(C-Ⅳ),alanine aminotransferase(ALT),and aspartate aminotransferase(AST),were measured,and the non-invasive indices APRI and FIB-4 were calculated.Peripheral blood levels of LncRNA Meg3,Beclin-1 and LC3B were detected using RT-qPCR,and liver stiffness(LSM)and shear wave velocity(SWV)were evaluated using two-dimensional shear wave elastography(2D-SWE).The liver tissues from 10 WD patients and 10 patients with hepatic hemangioma were examined using histochemical staining,transmission electron microscopy,and RT-qPCR.Results The expression level of LncRNA Meg3 was significantly lower,while the levels of AST,ALT,HA,LN,PIIINP,C-Ⅳ,APRI,FIB-4,LSM and SWV were significantly higher in WD patients than in the healthy individuals(all P<0.01).LncRNA Meg3 was negatively correlated with LSM,SWV,APRI,FIB-4,Beclin-1 and LC3B(P<0.05).ROC analysis demonstrated that LncRNA Meg3 effectively discriminated>F4 stage fibrosis(AUC=0.902)with a sensitivity of 92.9%and a specificity of 83.7%at the optimal cut-off value,outperforming APRI(AUC=0.746)and FIB-4(AUC=0.661).The liver tissues from WD patients exhibited characteristic histopathological changes and lowered expression of LncRNA Meg3,which was negatively correlated with Beclin-1 and LC3B expressions(P<0.05).Liver fibrosis staging(7 S4 cases and 3 S3 cases)was significantly associated with LSM and SWV levels(P<0.05).Conclusion The expression level of LncRNA Meg3 is significantly decreased in WD patients,which is negatively correlated with the severity of liver fibrosis and closely related to the level of autophagy.