MIR-92 stimulates VEGF by inhibiting von Hippel-Lindau gene product in epithelial ovarian cancer.

MIR-92 stimulates VEGF by inhibiting von Hippel-Lindau gene product in epithelial ovarian cancer. J Biol Regul Homeost Agents. 2017 Jul-Sep,;31(3):615-624 Authors: Guo FJ, Shao YP, Wang YP, Jin YM, Liu SS, Wang QY Abstract The molecular mechanisms underlying regulation of vascular endothelial growth factor (VEGF) in epithelial ovarian cancer (EOC) remain poorly defined. VEGF, a potent angiogenic factor, is up-regulated in a variety of cancers and contributes to angiogenesis in tumor tissues. The level of VEGF correlates with progression of malignancy. We previously reported that miR-92 is abnormally elevated in the plasma of EOC patients. Here, we tested the hypothesis that miR-92 inhibits von Hippel-Lindau gene product (VHL), a tumor suppressor gene, and in turn de-represses HIF-1α, a known key transcription factor for VEGF, to stimulate VEGF expression. Using a variety of biomedical methods including Western blot, RT-PCR, gene silencing, luciferase assay, and chromatin immunoprecipitation in both surgically-resected specimens and EOC cell culture, we established that EOC cells have elevated levels of HIF-1α and miR-92 expression, but the expression of VHL is reduced. We further demonstrated that miR-92 can target the VHL transcript to repress its expression. We also found that stabilized HIF-1α can form an active complex with transcriptional coactivator p300 and phosphorylated-STAT3 at the VEGF promoter to stimulate its expressi...
Source: Journal of Biological Regulators and Homeostatic Agents - Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research