UNLABELLED: As the "master" microRNA that is induced by hypoxia, miR-210 is involved in multiple processes in the hypoxia pathway. However, whether miR-210 mediates hypoxia-induced tumor cell metastasis still remains unclear. Here, we demonstrate that miR-210 is frequently up-regulated in hepatocellular carcinoma (HCC) samples and promotes the migration and invasion of HCC cells. Furthermore, miR-210 can be induced by hypoxia in HCC cells and mediates hypoxia-induced HCC cell metastasis. We identify vacuole membrane protein 1 (VMP1) as the direct and functional downstream target of miR-210; in addition, we show that its expression is negatively correlated with the expression of miR-210 in HCC. Intriguingly, VMP1 is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia-induced HCC cell metastasis. CONCLUSION: These findings extend our understanding of the function of miR-210 in the hypoxia pathway, and this newly identified hypoxia/miR-210/VMP1 pathway should facilitate the development of novel therapeutics against hypoxic tumor cells.
UNLABELLED: As the "master" microRNA that is induced by hypoxia, miR-210 is involved in multiple processes in the hypoxia pathway. However, whether miR-210 mediates hypoxia-induced tumor cell metastasis still remains unclear. Here, we demonstrate that miR-210 is frequently up-regulated in hepatocellular carcinoma (HCC) samples and promotes the migration and invasion of HCC cells. Furthermore, miR-210 can be induced by hypoxia in HCC cells and mediates hypoxia-induced HCC cell metastasis. We identify vacuole membrane protein 1 (VMP1) as the direct and functional downstream target of miR-210; in addition, we show that its expression is negatively correlated with the expression of miR-210 in HCC. Intriguingly, VMP1 is reduced by hypoxia, and down-regulation of VMP1 by miR-210 mediates hypoxia-induced HCC cell metastasis. CONCLUSION: These findings extend our understanding of the function of miR-210 in the hypoxia pathway, and this newly identified hypoxia/miR-210/VMP1 pathway should facilitate the development of novel therapeutics against hypoxic tumor cells.
Authors: Lauren Anton; Anthony O Olarerin-George; Nadav Schwartz; Sindhu Srinivas; Jamie Bastek; John B Hogenesch; Michal A Elovitz Journal: Am J Pathol Date: 2013-09-10 Impact factor: 4.307
Authors: H Cui; B Seubert; E Stahl; H Dietz; U Reuning; L Moreno-Leon; M Ilie; P Hofman; H Nagase; B Mari; A Krüger Journal: Oncogene Date: 2014-09-29 Impact factor: 9.867