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Cholangiocarcinoma is a highly aggressive malignant tumor disease with the increasing incidence and mortality. It’s urgent to identify specific biomarkers for cholangiocarcinoma treatment and diagnosis. Recent studies have noted the importance of lncRNAs in cancer and the following downstream mechanism with miRNAs network has been a hotspot. This work aimed to discover the role of lncRNA HCG18 and its possible downstream mechanism in cholangiocarcinoma tumor progression. Initially, through bioinformatics tools, we observed abnormal expression of lncRNA HCG18 in cholangiocarcinoma. In vitro experiments like (CCK-8, EdU, colony formation, flow cytometry, transwell, wound healing assays) and animal study confirmed that lncRNA HCG18 served as a cancer-promoting gene, promoted cancer proliferation, migration and invasion abilities. Besides, we found cancer cell-secreted exosomes transitted HCG18 to surrounding tumor cells and accelerated tumor growth and metastasis. After that, we confirmed HCG18 directly interacted with miR-424-5p through FISH, RIP and dual luciferase reporter assays with negative modulation. The inhibition of miR-424-5p reversed the HCG18 knockdown induced suppression on cholangiocarcinoma cancer cells. More specific, miR-424-5p targeted to SOX9 contributed to cholangiocarcinoma growth and metastasis through mediating PI3K/AKT pathway. In conclusion, these findings provide solid evidence of lncRNAs/miRNAs regulation in cholangiocarcinoma progression.

ABSTRACTCholangiocarcinoma (abbreviated as CCA) accounts for about 3% of digestive tract tumors, which is a rare disease with relatively low incidence. Herein, we firstly discovered overexpression of microRNA-23a-3p (abbreviated as miR-23a-3p) in CCA tissues, as well as cell lines via bioinformatics prediction. Next, by conducting miR-23a-3p knockdown system in HUCCT1 cells and miR-23a-3p overexpression system in RBE cells, we investigated the biological effects of miR-23a-3p. Based on our findings, inhibition of miR-23a-3p was able to prevent cancer cell proliferation via colony formation, CCK-8, as well as EdU assays. Moreover, invasion as well as migration abilities of cells was examined by transwell assay and wound healing test. Animal study further verified that knockdown miR-23a-3p slowed down tumor growth and lung metastasis. In addition, we identified cholangiocarcinoma cells transferred miR-23a-3p through exosomes by a series of assays. Functional experiments have confirmed that exosomal miR-23a-3p could benefit for cancer cell growth and metastasis, serving as a cancer promoting gene. Furthermore, we found Dynamin3 (abbreviated as DNM3) turned out to be a target of miR-23a-3p, while DNM3 was down-regulated in cholangiocarcinoma. Knockdown DNM3 accelerated cancer cell development. Collectively, our findings firstly pointed out that exosomal miR-23a-3p was conducive to the progression of cholangiocarcinoma by interaction with DNM3, which provided potential evidence for cancer treatment.