Effect of MiR-145/HMGB3 Axis on Diagnosis and Prognosis of Patients with Gallbladder Cancer and Apoptosis of Gallbladder Cancer Cells
Objective To investigate the expression levels of serum miR-145 and HMGB3 in patients with gallbladder cancer(GBC)and their correlation with disease progression,verify the effects of miR-145 on HMGB3 expression and the proliferation and ap-optosis of GBC cells,and evaluate its feasibility as a potential diagnostic and prognostic biomarker.Methods Ninety patients with gall-bladder cancer admitted to the First Affiliated Hospital of Hebei North University from September 2018 to June 2022 were selected as the disease group,and 40healthy subjects were selected as the normal control group.The expression levels of serum miR-145 and HMGB3 in two groups were detected.The relationship between different clinicopathological features and the expression levels of miR-145 and HMGB3 was compared.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum miR-145 and HMGB3;Kaplan-Meier survival curve was used to evaluate the 3-year survival rate of patients with different miR-145 and HMGB3 ex-pression levels.The effects of miR-145 on proliferation and apoptosis of GBC cells were analyzed by CCK-8 assay and flow cytometry.The protein expression was detected by Western blot.The apoptosis rate of each group was detected by flow cytometry.The direct interac-tion between miR-145 and HMGB3 was verified by double luciferase reporter gene assay.Results The expression level of miR-145 in serum of patients with GBC was significantly decreased(P＜0.05),while the expression level of HMGB3 was significantly increased(P＜0.05).The expressions of serum miR-145 and HMGB3 were correlated with differentiation degree,lymph node metastasis and TNM stage(P＜0.05).ROC curve analysis showed that serum miR-145 and HMGB3had high diagnostic value.Kaplan-Meire survival curve analysis showed that the 3-year survival rate of miRNA-143high expression subgroup was higher than that of low expression sub-group(P＜0.05),and the 3-year survival rate of HMGB3 low expression subgroup was significantly higher than that of high expression subgroup(P＜0.05).Overexpression of miR-145 inhibited the proliferation of GBC cells,significantly increased the expression of Bax protein in BGC-SD cells(P＜0.05),decreased the expression of Bel-2 protein(P＜0.05),decreased the expression of HMGB3 pro-tein(P＜0.05),and increased the apoptosis rate of BGC-SD cells.Double luciferase reporter gene assay showed that HMGB3 was the target of miR-145.Conclusion The downregulation of miR-145 is significantly associated with the upregulation of HMGB3 in GBC,and is related to the severity of the disease.Overexpression of miR-145 can significantly inhibit the proliferation and promote apoptosis of GBC cells,and the mechanism of action may be achieved by directly targeting HMGB3.Therefore,miR-145 and HMGB3may serve as potential biomarkers for the diagnosis and prognosis of GBC,providing a new strategy for molecular targeted therapy of GBC.
万方数据
维普
