%0 Journal Article
%T Suppression of vascular endothelial growth factor expression in breast cancer cells by microRNA-125b-mediated attenuation of serum amyloid A activating factor-1 level
%A Alpana Ray
%A Bimal K. Ray
%J Archive of "Oncoscience".
%D 2019
%R 10.18632/oncoscience.483
%X Increased level of an inflammation-responsive transcription factor called serum amyloid A-activating factor (SAF-1) has been linked to the pathogenesis in human breast cancer. SAF-1 is found to promote vascular endothelial growth factor (VEGF) expression in breast carcinoma cells and boost angiogenesis. In an effort to develop a cellular mechanism to control VEGF expression, we sought to limit SAF-1 activity in breast cancer cells. We report here several targets within the SAF-1 mRNA for binding of microRNA-125b (miR-125b) and we show that VEGF expression is reduced in breast cancer cells when SAF-1 level is reduced with the microRNA action. Within the 3' un-translated region (UTR) of SAF-1 transcript, we have identified four highly conserved miR-125b responsive elements. We show that these miR-125b binding sites mediate repression of SAF-1 by miR-125b. Ectopic expression of miR-125b in nonmetastatic and metastatic breast cancer cells repressed SAF-1-mediated activity on VEGF promoter function and inhibited cancer cell migration and invasion potentials in vitro. Together, these results suggest that termination of SAF-1 function by miR-125b could be developed as a potential anti-VEGF and anti-angiogenic agent, which has high clinical relevance
%K Breast cancer
%K SAF-1
%K miR-125b
%K transcriptional regulation
%K VEGF expression
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650169/