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

Abstract

Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor derived from intrahepatic bile duct epithelial cells. Accumulating studies report that mi-croRNAs 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. Methods: The 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. Results: Our 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. Conclusions: The 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.

Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3

“…The roles of other miRNAs in CCA have been reported previously: there is upregulation of miR-181b-5p 22 and miR-23a-3p 23 in human CCA tissues and of miR-196-5p in CCA cell lines 24 . On the other hand, miRNA-206 is downregulated in CCA cell lines 25 , miR-7-5p in intrahepatic CCA tissue and cell lines 26 , and miR-451 in human tissues and serum 27 in CCA patients compared with normal subjects. As the most upregulated miRNA of the ten miRNAs previously reported to be elevated, miR-205-5p was more abundant in exosomes isolated from KKU-M213 and HuCCA-1 cell lines than in exosomes isolated from the H69 CCA cell line 28 .…”

Differentially expressed non-coding RNAs and their regulatory networks in liver cancer

“…As for ICC, cancer tissue and HCCC-9810 cell line, the level of oncogenic miR-31 has been reported to significantly increase to target RAS p21 GTPase activating protein 1, and this promoted cell proliferation via Ras-MAPK signaling pathway [ 46 ]. Whereas, miR-7-5p has been shown to negatively regulate ICC cell proliferation, migration, and invasion via targeting myeloid differentiation factor 88 [ 47 ]. Also, miR-424-5p has been observed to target AMPK-related protein kinase 5; it is downregulated in ICC tissues and this stimulates the invasion, migration and EMT progression of ICC [ 48 ].…”

Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review)

“…Based on certain preclinical studies that have identified the potential therapeutic effects of drugs targeting the STaT signal transduction pathway, the development of highly effective and well-tolerated drugs is anticipated in the future. The molecular mechanism of icc requires further exploration (101), which will facilitate the application of specific genes and signalling pathways to the classification of icc molecular subtypes and the development of targeted therapeutic drugs. Further studies are required to take advantage of multidisciplinary comprehensive treatment, including surgery, chemotherapy and targeted therapy, according to the molecular characteristics of icc in order to improve the quality of life and prolong the survival time of patients.…”