PMID- 27245201 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20170306 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 38 IP - 1 DP - 2016 Jul TI - Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells. PG - 236-42 LID - 10.3892/ijmm.2016.2621 [doi] AB - BCL2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock 70 kDa protein (HSPA) family of proteins, is a cytoprotective protein that acts against various stresses, including heat stress. The aim of the present study was to identify gene networks involved in the enhancement of hyperthermia (HT) sensitivity by the knockdown (KD) of BAG3 in human oral squamous cell carcinoma (OSCC) cells. Although a marked elevation in the protein expression of BAG3 was detected in human the OSCC HSC-3 cells exposed to HT at 44 C for 90 min, its expression was almost completely suppressed in the cells transfected with small interfering RNA against BAG3 (siBAG) under normal and HT conditions. The silencing of BAG3 also enhanced the cell death that was increased in the HSC-3 cells by exposure to HT. Global gene expression analysis revealed many genes that were differentially expressed by >2-fold in the cells exposed to HT and transfected with siBAG. Moreover, Ingenuity(R) pathways analysis demonstrated two unique gene networks, designated as Pro-cell death and Anti-cell death, which were obtained from upregulated genes and were mainly associated with the biological functions of induction and the prevention of cell death, respectively. Of note, the expression levels of genes in the Pro-cell death and Anti-cell death gene networks were significantly elevated and reduced in the HT + BAG3-KD group compared to those in the HT control group, respectively. These results provide further insight into the molecular mechanisms involved in the enhancement of HT sensitivity by the silencing of BAG3 in human OSCC cells. FAU - Yunoki, Tatsuya AU - Yunoki T AD - Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. FAU - Tabuchi, Yoshiaki AU - Tabuchi Y AD - Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama 930-0194, Japan. FAU - Hayashi, Atsushi AU - Hayashi A AD - Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. FAU - Kondo, Takashi AU - Kondo T AD - Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. LA - eng PT - Journal Article DEP - 20160531 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BAG3 protein, human) RN - 0 (RNA, Messenger) SB - IM MH - Adaptor Proteins, Signal Transducing/*genetics/metabolism MH - Apoptosis Regulatory Proteins/*genetics/metabolism MH - Carcinoma, Squamous Cell/*genetics MH - Cell Death MH - Cell Line, Tumor MH - Cell Proliferation MH - Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - *Gene Knockdown Techniques MH - *Gene Regulatory Networks MH - Humans MH - *Hyperthermia, Induced MH - Mouth Neoplasms/*genetics MH - RNA, Messenger/genetics/metabolism EDAT- 2016/06/02 06:00 MHDA- 2017/03/07 06:00 CRDT- 2016/06/02 06:00 PHST- 2015/11/25 00:00 [received] PHST- 2016/05/16 00:00 [accepted] PHST- 2016/06/02 06:00 [entrez] PHST- 2016/06/02 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - 10.3892/ijmm.2016.2621 [doi] PST - ppublish SO - Int J Mol Med. 2016 Jul;38(1):236-42. doi: 10.3892/ijmm.2016.2621. Epub 2016 May 31.