title: Down-regulation of HMGB1 expression by shRNA constructs inhibits the bioactivity of urothelial carcinoma cell lines via the NF-κB pathway.
abstract: The high mobility group box 1 (HMGB1), which is a highly conserved and evolutionarily non-histone nuclear protein, has been shown to associate with a variety of biological important processes, such as transcription, DNA repair, differentiation, and extracellular signalling. High HMGB1 expression has been reported in many cancers, such as prostate, kidney, ovarian, and gastric cancer. However, there have been few studies of the function of HMGB1 in the malignant biological behaviour of bladder urothelial carcinoma (BUC), and the potential mechanism of HMGB1 in the pathogenesis of BUC remains unclear. Thus, in this study, we constructed plasmid vectors that are capable of synthesizing specific shRNAs targeting HMGB1 and transfected them into BUC cells to persistently suppress the endogenous gene expression of HMGB1. The expression of HMGB1, the bioactivity of BUC cells, including proliferation, apoptosis, cell cycle distribution, migration and invasion, and the effects of HMGB1 knockdown on downstream signalling pathways were investigated. Our data suggest that HMGB1 promotes the malignant biological behaviour of BUC, and that this effect may be partially mediated by the NF-κB signalling pathway. HMGB1 may serve as a potential therapeutic target for BUC in the future.
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongshan Hospital, Xiamen University, Xiamen 361004, Fujian, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Shanbiao
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D034741:RNA, Small Interfering; D042582:Vascular Endothelial Growth Factor C; D000072000:NF-KappaB Inhibitor alpha