Abstract
Systems biology is gaining importance in studying complex systems such as the functional interconnections of human genes [1]. To investigate the molecular interactions involved in T cell immune responses, we used databases of physical gene-gene interactions to constructed molecular interaction networks (interconnections) with R language algorithms. This helped to identify highly interconnected "hub" genes AT(1)P5C1, IL6ST, PRKCZ, MYC, FOS, JUN, and MAPK1. We hypothesized that suppression of these hub genes in the gene network would result in significant phenotypic effects on T cells and examined this in vitro. The molecular interaction networks were then analyzed and visualized with Cytoscape. Jurkat and HeLa cells were transfected with siRNA for the selected hub genes. Cell proliferation was measured using ATP luminescence and BrdU labeling, which were measured 36, 72, and 96 h after activation. Following T cell stimulation, we found a significant decrease in ATP production (P < 0.05) when the hub genes ATP5C1 and PRKCZ were knocked down using siRNA transfection, whereas no difference in ATP production was observed in siRNA transfected HeLa cells. However, HeLa cells showed a significant (P < 0.05) decrease in cell proliferati...Continue Reading
References
May 15, 1977·International Journal of Cancer. Journal International Du Cancer·U SchneiderG Bornkamm
Jan 11, 2000·Nucleic Acids Research·G D BaderC W Hogue
Jul 2, 2002·Nature Medicine·Roger J Pomerantz
Sep 24, 2002·Nature Biotechnology·Haibin XiaBeverly L Davidson
Mar 15, 2003·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·G Mukherjee, S S Manna
Oct 23, 2004·Science·Leroy HoodBiaoyang Lin
May 24, 2005·Cell·Marc W Kirschner
May 10, 2006·PLoS Medicine·Andrew C AhnRussell S Phillips
Aug 15, 2006·Immunological Reviews·Maria Grazia RoncaroloMegan K Levings
Dec 29, 2006·Blood·Patrizia CavadiniPaolo Arosio
Apr 18, 2007·Molecular Systems Biology·Xin LuDavid L Perkins
Jun 30, 2007·Journal of Internal Medicine·B T Rouse
Oct 20, 2007·Nature Protocols·Melissa S ClineGary D Bader
Oct 31, 2007·Nature Clinical Practice. Rheumatology·Xavier Valencia, Peter E Lipsky
Feb 19, 2008·Pharmacology & Therapeutics·Vipul V JainPatricia W Finn
Mar 5, 2008·Clinical & Developmental Immunology·Nathalie CoolsZwi N Berneman
Mar 30, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P F Halloran
Dec 24, 2010·Vox Sanguinis·D Charron
Citations
Apr 17, 2012·The Journal of Surgical Research·Reza F Saidi
Nov 29, 2015·Asian Pacific Journal of Tropical Medicine·Xiao-Wen LiGuzhalinuer Abulizi
Aug 8, 2014·Clinical and Experimental Medicine·Shivtia Trop-SteinbergReuven Or
Oct 9, 2014·Frontiers in Neurology·He LiRobert Ursano
Oct 3, 2018·International Journal of Molecular Medicine·Yong YangXiu-Tian Guo
Apr 11, 2017·Oncology Reports·Wenfeng LiRongying Ou
Dec 15, 2020·Current Opinion in Organ Transplantation·Sunil M KurianChristopher L Marsh