| Experiment ID | EXP00222 |
| Reference | Title: MicroRNA-214 downregulation contributes to tumor angiogenesis by inducingsecretion of the hepatoma-derived growth factor in human hepatoma. Author: Shih TC, Tien YJ, Wen CJ, Yeh TS, Yu MC, Huang CH, Lee YS, Yen TC, Hsieh SY. Journal: J Hepatol. 2012 Sep;57(3):584-91. doi: 10.1016/j.jhep.2012.04.031. Epub 2012 May 18. Abstract: BACKGROUND & AIMS: Unusual hypervascularity is a hallmark of human hepatocellularcarcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other humancancers, it is downregulated in HCC. We elucidated the biological and clinicalsignificance of miR-214 downregulation in HCC.METHODS: MicroRNAs deregulated in HCC were identified using array-based microRNA profiling. A luciferase reporter assay confirmed target association betweenmiR-214 and the hepatoma-derived growth factor (HDGF). Tube formation and in vivoangiogenesis assays validated the roles of miR-214/HDGF in angiogenesis.RESULTS: miR-214 downregulation was associated with higher tumor recurrence andworse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumorgrowth and microvascularity of the tumors and their surrounding tissues. Thegenes downregulated by ectopic expression of miR-214 were involved in theregulation of apoptosis, cell cycle, and angiogenesis. Integrated analysisdisclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cellscontained bioactivity to stimulate tube formation of human umbilical veinendothelial cells, which was abolished by pretreatment of the conditioned mediawith HDGF antibodies, suppression of HDGF expression or ectopic expression ofmiR-214 in the donor HCC cells. The angiogenic activity of the conditioned media,lost by ectopic expression of miR-214 in the donor cells, was restored bysupplementation with recombinant HDGF. In vivo tumor angiogenesis assays showedsignificant suppression of tumor vascularity by ectopic expression of miR-214.CONCLUSIONS: A novel role of microRNA in tumorigenesis is identified.Downregulation of miR-214 contributes to the unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis. PMID: 22613005 |
| Expressiion Profile | Description: MicroRNA-214 downregulation contributes to tumor angiogenesis via inducing secretion of hepatoma-derived growth factor in human hepatoma Organism: Homo sapiens GEO ID: GSE36915 Platform: GPL8179 Number of samples: 89 |
| Design and Sample | Cancer Type: hepatocellular carcinoma Cancer SubType: N/D Cell Line: N/D Experimental Design: high grade vs low grade Case Sample: hepatocellular carcinoma stage T3a Control Sample: hepatocellular carcinoma stage T1 Num of Case: 26 Num of Control: 26 Quantification Software: Limma Num of miRNAs: 846 |
| Identification | Num of Up: 26 Num of Down: 34 |