title: Microarray-based gene expression profiling reveals genes and pathways involved in the oncogenic function of REG3A on pancreatic cancer cells.
abstract: We previously reported that regenerating islet-derived protein 3 alpha (REG3A) exacerbates pancreatic malignancies. The mechanism of this effect has not been clearly elucidated. Here we first identified key differentially expressed genes (DEGs) and signal pathways in the pancreatic cancer cell line SW1990, compared to two control cell lines, by microarray analysis. We then identified key genes and pathways regulated by REG3A or the cytokine IL6 in SW1990 cells. Afterwards, these DEGs induced by REG3A or IL6 were subjected to KEGG pathway enrichment analysis and GO function analysis by the DAVID online tool. Ultimately, we constructed protein-protein interaction networks among the DEGs by Cytoscape. Among the three pancreatic cell lines, SW1990 exhibited highly deterioration with the activation of genes and pathways related to proliferation, survival, angiogenesis, and invasion. As a result, 50 DEGs enriched in 11 pathways were identified in REG3A-treated SW1990 cells, and 28 DEGs enriched in 9 pathways were detected in IL6-treated cells. Overall, results of microarray analysis followed by qRT-PCR and Western blotting suggest that REG3A regulates pancreatic cell growth by increasing the expression of at least 8 genes: JAK1, STAT3, IL10, FOXM1, KRAS, MYC, CyclinD1, and c-fos; and activation of at least 4 signal pathways: TGFβ, PDGF, angiogenesis and RAS. Similar results were obtained with IL6 treatment. Regulation network analysis confirmed the cell growth related DEGs, and further uncovered three transcription factor families with immune functions regulated by REG3A.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Guoxiao
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, School of Life Science, Wuchang University of Technology, Wuhan 430223, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: xiangming@mails.tjmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics*; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D037181:Lectins, C-Type; D009363:Neoplasm Proteins; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human
keywords: Differentially expressed genes; Pancreatic cancer; Proliferation; REG3A