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miR‐885‐5p inhibits proliferation and metastasis by targeting IGF2BP1 and GALNT3 in human intrahepatic cholangiocarcinoma
Author(s) -
Lixin Sun,
Wei Sun,
Haibin Song,
Qingfu Lang,
Tiemin Pei
Publication year - 2020
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23262
Subject(s) - downregulation and upregulation , biology , metastasis , gene silencing , microrna , cancer research , pi3k/akt/mtor pathway , protein kinase b , cell growth , carcinogenesis , signal transduction , cancer , microbiology and biotechnology , gene , genetics
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.