miR‐885‐5p inhibits proliferation and metastasis by targeting IGF2BP1 and GALNT3 in human intrahepatic cholangiocarcinoma

• Published in: Molecular carcinogenesis Vol. 59; no. 12; pp. 1371 - 1381
• Main Authors: Lixin, Sun, Wei, Sun, Haibin, Song, Qingfu, Lang, Tiemin, Pei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2020
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; GALNT3; Gene Expression Regulation, Neoplastic; Humans; IGF2BP1; Insulin; intrahepatic cholangiocarcinoma; Lymph nodes; Male; Metastases; Metastasis; Mice; MicroRNAs - genetics; miRNA; miR‐885‐5p; mRNA; N-Acetylgalactosaminyltransferases - genetics; N-Acetylgalactosaminyltransferases - metabolism; Neoplasm Metastasis; Neoplasm Transplantation; Polypeptide N-acetylgalactosaminyltransferase; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Signal transduction; Survival Analysis; IGF2BP1; GALNT3; miR-885-5p; intrahepatic cholangiocarcinoma
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23262

The incidence of intrahepatic cholangiocarcinoma (iCCA) continues to increase worldwide, however its molecular pathogenesis remains poorly understood. Recent studies have implicated microRNAs in iCCA progression. In this study, we demonstrated that miR‐885‐5p was significantly decreased in iCCA tissues. Downregulation of miR‐885‐5p was correlated with vascular invasion, lymph node metastasis, unfavorable overall survival, and shorter disease‐free survival. Silencing or overexpressing miR‐885‐5p by lentiviral approaches significantly influenced iCCA cell proliferation and metastasis in vitro and in vivo. Mechanistically, overexpression of miR‐885‐5p inhibited iCCA metastasis and proliferation by directly inhibiting GALNT3 as well as by indirectly promoting the downregulation of insulin‐like growth factor‐2 mRNA‐binding protein 1 (IGF2BP1). Furthermore, miR‐885‐5p inhibited iCCA metastasis by downregulating the PI3K/AKT/MMPs signaling pathway via targeting GALNT3. Collectively, we demonstrated that miR‐885‐5p was an important mediator of iCCA proliferation and metastasis by regulating GALNT3 and IGF2BP1, thus offering a potential target for iCCA treatment.