miR-6883 downregulates HIF1α in colorectal and breast cancer cells

Abstract

Colorectal cancer (CRC) and breast cancer (BC) are deadly diseases that rank as the second and fourth leading causes of cancer-related deaths, respectively. We have previously shown that miR-6883 targets CDK4/6 and that palbociclib-mediated CDK4/6 inhibition destabilizes HIF1. We hypothesize that miR-6883 downregulates HIF1 in CRC and BC cells. miR-6883 was transfected under normoxia or hypoxia and western blot analysis revealed that miR-6883 downregulates CDK4/6 and HIF1 in CRC and BC cells, pointing to miR-6883 as a promising therapeutic to target hypoxic cancers or HIF1-deregulated tumor cells. Future studies will further investigate miR-6883 as a cancer biomarker, effects on HIF-related proteins and therapeutic uses in vivo. O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/556385v1_fig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@e0acadorg.highwire.dtl.DTLVardef@68b428org.highwire.dtl.DTLVardef@bc4dforg.highwire.dtl.DTLVardef@aa13ad_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO miR-6883 downregulates CDK4/6 and HIF1 in colorectal and breast cancer cells A) Colorectal cancer cells were treated with doses of palbociclib ranging from 0-20 {micro}M. Cell viability was measured by imaging the bioluminescent signal after addition of CellTiter-Glo reagent. B) Percent viability of colorectal cancer cells treated with palbociclib was calculated and nonlinear regression analysis was completed using GraphPad Prism software. C-H) CRC cells were transfected with miR-6883 under normoxia or hypoxia (<0.5% O2) and protein levels of CDK4/6, HIF1, Glut1, and Ran were measured by Western blot. C_FIG