Citations 1
Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis
Joshi, Hemant , Subramanian, Indira V., Schnettler, Erica, Rupaimoole, Rajesha , Evans, Colleen, Saluja, Manju, Jing, Yawu, Ivan, Cristina , Shah, Vijay H. , Ramakrishnan, Sundaram , Ghosh, Goutam , Roy, Sabita , Zeng, Yan , Sood, Anil K.
Proceedings of the National Academy of Sciences | March 25, 2014 | Volume: 111 | Issue: 14 | Pages: 5331-5336
Significance Tumor cells adapt to hypoxia by modulating energy production and utilization. Endocytosis is an energy-consuming process that is suppressed during hypoxia. Our studies show that Dynamin 2 (DNM2), a key component of endocytic machinery, is transcriptionally suppressed by HIF-1. Genetic and pharmacological inactivation of DNM2 stabilized HIF-1α and HIF-2α. Furthermore, miR-199a, which is encoded from the opposite strand of DNM2 , exerts reciprocal negative regulation upon HIF-1α and HIF-2α. Overexpression of miR-199a decreased HIF-1α and HIF-2α, cell migration, and metastasis. These findings establish a regulatory loop between endocytic pathway and hypoxic response in tumor cells.