MicroRNA-7-5p Inhibits Migration, Invasion and Metastasis of Intrahepatic Cholangiocarcinoma by Inhibiting MyD88.

Abstract

Background and AimsIntrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that microRNAs are widely involved in tumor migration and metastasis by regulation of target genes. miR-7-5p has been confirmed to inhibit tumor metastasis and to be related to prognosis for several malignant tumors. Our study investigated the underlying functions of miR-7-5p in ICC.MethodsThe expression of miR-7-5p in ICC tissues but also in ICC cell lines was analyzed by real-time PCR. By analyzing the relationship between the clinicopathological parameters of 60 ICC patients and the expression level of miR-7-5p, the effect of miR-7-5p on the prognosis was clarified. After transfected with miR-7-5p mimics or miR-7-5p inhibitor, cell counting kit-8 assay was applied to evaluate the cells proliferation, flow cytometry was applied to analyze the cells apoptosis, wound healing assay and transwell chamber assay were applied to analyze the cell invasion and migration. A luciferase reporter assay was identified the relationship of miR-7-5p and myeloid differentiation factor 88 (MyD88). Western blotting was used to analyze the proteins expression. And immunochemistry was performed to determine the expression of MYD88 in ICC tissues.ResultsOur data showed the expression of miR-7-5p was down-regulated not only in ICC tissues but also in ICC cell lines compared with normal controls. Low expression of miR-7-5p was notably associated with poor prognosis in ICC patients. miR-7-5p negatively regulated cell proliferation, migration, invasion and apoptosis in ICC cells. We further verified that MyD88 was a novel target of miR-7-5p and was significantly overexpressed in ICC tissues. Overexpression of MyD88 counteracted the effects of miR-7-5p in ICC cells.ConclusionsThe present findings suggest that miR-7-5p plays a pivotal role in ICC invasion by regulating MyD88. Ampliative insight into the key factors of ICC invasion may result in the development of new treatment options for ICC.