Decreased expression of hsa-MIR-372 predicts poor prognosis in patients with gallbladder cancer by affecting chloride intracellular channel 1

Abstract

It has been reported that hsa-microRNA (miRNA/miR)-372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa-MIR-372 in GBC. The expression of hsa-MIR-372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription-quantitative polymerase chain reaction. Subsequently, the associations between hsa-MIR-372 expression levels and the clinicopathological characteristics of patients with GBC were determined using Χ2 test. Furthermore, Kaplan-Meier method and Cox regression analysis were performed to evaluate the association between hsa-MIR-372 expression and the prognosis of patients with GBC. Furthermore, a dual-luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa-MIR-372. The results demonstrated that markedly lower hsa-MIR-372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa-MIR-372 was negatively associated with tumor histological grade, tumor-node-metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa-MIR-372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa-MIR-372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa-MIR-372. In conclusion, the current study provides the frst statistically convincing evidence that downregulation of hsa-MIR-372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression.