Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis

• DOI: 10.1073/pnas.1317242111
• Publication Date: 2014-03-25T05:25:24Z
• Authors: Hemant P. Joshi; Indira V. Subrama...; Erica K. Schnettler; Goutam Ghosh; Rajesha Rupaimoole; Colleen Evans; Manju Saluja; Yawu Jing; Ivan Cristina; Sabita Roy; Yan Zeng; Vijay H. Shah; Anil K. Sood; Sundaram Ramakris...
• Keywords: Hypoxia

Hypoxia-driven changes in the tumor microenvironment facilitate cancer metastasis. In present study, we investigated regulatory cross talk between endocytic pathway, hypoxia, and Dynamin 2 (DNM2), a GTPase, is critical mediator of endocytosis. Hypoxia decreased levels DNM2. DNM2 promoter has multiple hypoxia-inducible factor (HIF)-binding sites genetic deletion them relieved hypoxia-induced transcriptional suppression. Interestingly, reciprocally regulated HIF. Inhibition GTPase activity dominant-negative mutant showed functional role for regulating Furthermore, opposite strand gene encodes miR-199a, which similarly reduced cells under hypoxia. miR-199a targets 3'-UTR HIF-1α HIF-2α. Decreased expression hypoxia increased HIF levels. Exogenous HIF, cell migration, metastasis ovarian cells. miR-199a-mediated affected matrix-remodeling enzyme, lysyloxidase (LOX). LOX negatively correlated with progression-free survival patients. These results demonstrate relationship DNM2, implications