Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8435086 | Cancer Letters | 2018 | 40 Pages |
Abstract
Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231Â cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (>2.0 fold) in CNOT2 depleted MDA-MB-231Â cells compared to untreated control. Consistently, downregulation of VEGF, CNOT2 and HIF2 alpha was verified in CNOT2 depleted MDA-MB-231Â cells by RT-qPCR. Additionally, CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and reduced neovascularization in CAM assay. Furthermore, the growth of CNOT2 depleted MDA-MB-231Â cells was significantly reduced in Balb/c nude mice along with decreased expression of VEGF and PCNA by immunohistochemistry compared to untreated control group. Overall, our findings provide evidences that CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells as a potent molecular target for breast cancer treatment.
Keywords
EGFRCCR4-Not complexGSK3α/βPPAR γHIPK2autophagy-related gene 5ATG5TBSTRT-qPCRHUVECSHRPTNBCHER2PBSFBSDMEMC/EBPαDulbecco's modified Eagle's mediumTissue arraychromatin immunoprecipitationCAMTriple negative breast cancersBreast cancerfetal bovine serumHuman umbilical vein endothelial cellsChick chorioallantoic membraneVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Phosphate-buffered salinereal-time polymerase chain reactionHorseradish peroxidaseCHiPHuman epidermal growth factor receptor 2Epidermal growth factor receptorperoxisome proliferator-activated receptor γ
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Eun Jung Sohn, Deok-Beom Jung, HyoJung Lee, In Han, Jihyun Lee, Hyemin Lee, Sung-Hoon Kim,