title: MicroRNA-101 inhibits the migration and invasion of intrahepatic cholangiocarcinoma cells via direct suppression of vascular endothelial growth factor-C.
abstract: MicroRNAs (miRs) have important roles in the pathogenesis of human malignancy. It has previously been suggested that deregulation of miR‑101 is associated with the progression of intrahepatic cholangiocarcinoma (ICC); however, the exact role of miR‑101 in the regulation of ICC metastasis remains largely unknown. The present study demonstrated that the expression levels of miR‑101 were significantly decreased in ICC tissue, as compared with matched adjacent normal tissue. Furthermore, miR‑101 was downregulated in the ICC‑9810 human ICC cell line, as compared with in the normal human intrahepatic biliary epithelial cell (HIBEC) line. Vascular endothelial growth factor (VEGF)‑C was identified as a target gene of miR‑101 in ICC‑9810 cells. The expression of VEGF‑C was negatively regulated by miR‑101 at the post‑transcriptional level in ICC‑9810 cells. Further investigation demonstrated that overexpression of miR‑101 markedly suppressed the migration and invasion of ICC‑9810 cells, and these effects were similar to those observed following VEGF‑C knockdown. Conversely, restoration of VEGF‑C reversed the inhibitory effects of miR‑101 overexpression on ICC‑9810 cell migration and invasion, thus suggesting that miR‑101 may suppress ICC‑9810 cell migration and invasion, at least partly via inhibition of VEGF‑C. It was also demonstrated that the mRNA and protein expression levels of VEGF‑C were frequently upregulated in ICC tissue and cells, and its expression level was inversely correlated with that of miR‑101 in ICC tissue. In conclusion, the present study identified important roles for miR‑101 and VEGF‑C in ICC, suggesting that miR‑101/VEGF‑C signaling may be a promising diagnostic and/or therapeutic target for ICC.
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Gang
authors: G
authors: Deng
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Yinglu
authors: Y
authors: Teng
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Feizhou
authors: F
authors: Huang
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Wanpin
authors: W
authors: Nie
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Lei
authors: L
authors: Zhu
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Wei
authors: W
authors: Huang
authors: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Hongbo
authors: H
authors: Xu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016415:Sequence Alignment; D015398:Signal Transduction; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D042582:Vascular Endothelial Growth Factor C