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.

中文翻译：

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miR‐885-5p通过靶向人肝内胆管癌的IGF2BP1和GALNT3抑制增殖和转移

肝内胆管癌（iCCA）的发病率在全球范围内持续增加，但是其分子发病机理仍然知之甚少。最近的研究表明microRNA与iCCA进展有关。在这项研究中，我们证明了iCCA组织中的miR-885-5p显着降低。miR-885-5p的下调与血管浸润，淋巴结转移，总体生存不良和无病生存期短有关。慢病毒方法沉默或过表达miR-885-5p会在体内外显着影响iCCA细胞的增殖和转移。从机制上讲，miR-885-5p的过表达通过直接抑制GALNT3以及间接促进胰岛素样生长因子-2 mRNA结合蛋白1（IGF2BP1）的下调来抑制iCCA的转移和增殖。此外，miR-885-5p通过靶向GALNT3来下调PI3K / AKT / MMPs信号通路，从而抑制了iCCA转移。我们共同证明，miR-885-5p通过调节GALNT3和IGF2BP1是iCCA增殖和转移的重要介体，从而为iCCA治疗提供了潜在的靶标。