tfpi alpha and beta regulate mrnas and micrornas involved in cancer biology and in the immune system in breast cancer cells活性因子α和β调节mrna和小分子核糖核酸参与癌症生物学和在乳腺癌细胞的免疫系统.pdf

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells 1,4 2 3 1 1 Benedicte Stavik , Grethe Skretting , Ole Kristoffer Olstad , Marit Sletten , Magnus Dehli Vigeland , 2,4 1 Per Morten Sandset , Nina Iversen * 1 Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway, 2 Department of Haematology and Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway, 3 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway, 4 Institute of Clinical Medicine, University of Oslo, Oslo, Norway Abstract Emerging evidence indicate a new role of TFPI in cancer biology. We recently reported that both isoforms of TFPI induced apoptosis and inhibited proliferation of cancer cells. The signaling pathway(s) mediating the effects of TFPI is, however, presently still unclear. Our goal was to further investigate the cellular processes affected by TFPI and to get insight into the molecular mechanisms involved in the effects of TFPI, using a global gene expression study approach. TFPIa or TFPIb cDNA were transfected into SK-BR-3 breast cancer cells for stable overexpression. Global mRNA and microRNA (miRNA) expressions were measured and functional annotation of the differentially expressed genes and miRNAs according to gene ontology terms was conducted. Selected results were validated using qRT-PCR and Western blot. A total of 242 and 801 mRNA transcripts and 120 and 46 miRNAs were differentially expressed in cells overexpressing TFPIa or TFPIb, respectively