Long non-coding RNA MIR22HG inhibits cell proliferation and migration in cholangiocarcinoma by negatively regulating the Wnt/β-catenin signaling pathway.

Abstract

Cholangiocarcinoma (CCA) is one of the most common primary biliary malignant tumors with a high mortality. MIR22HG has been reported to act as a tumor-suppressor gene in several types of cancers. However, the role and molecular regulatory mechanism of MIR22HG in CCA still remains unclear. The present study aimed to investigate the role and underlying mechanism of MIR22HG in CCA. The expression of MIR22HG was detected by RT-qPCR assayin CCA tissues and cells. CCK-8, colony formation and transwell assays were performed to study the biological function of MIR22HG in CCA. Western blot and immunofluorescence assays were performed to detect the expression ofWnt/β-catenin signaling pathway markers. In vivo assays were conducted to explore the biological role of MIR22HG. We first found that MIR22HG expression was significantly down-regulated in CCA tissues and cell lines. Moreover, MIR22HG expression was related to TNM stage and bore prognostic significance in CCA patients. Function experiments demonstrated that overexpression of MIR22HG inhibited cell proliferation, migration and invasion in CCA, whereas knockdown of MIR22HG caused the opposite result. It was found that MIR22HG negatively regulated mRNA and the expression levels of proteins in the Wnt/β-catenin signaling pathway (β-catenin, cyclin D1 and c-myc). The effect of MIR22HG overexpression on CCA progression could be partly rescued by activating the Wnt/β-catenin signaling pathway. MIR22HG suppressed CCA tumorigenesis in vivo. In summary, the results of the present study show that MIR22HG repressed cell proliferation, migration and invasion in CCA by negatively regulating the Wnt/β-catenin signaling pathway. MIR22HG may be a novel target for diagnosis and therapy in CCA.