title: Suppression of Cellular Proliferation and Invasion by HMGB1 Knockdown in Bladder Urothelial Carcinoma Cells.
abstract: HMGB1, which acts as a DNA chaperone to help maintain nuclear homeostasis, was reported to play a prominent role in cancer progression, angiogenesis, invasion, and metastasis development. Increased expression of HMGB1 has been observed in several tumor entities. However, the molecular mechanisms of HMGB1 in tumorigenesis of bladder cancer have rarely been reported. In the present study, real-time quantitative RT-PCR analysis revealed that the expression of HMGB1 in human bladder urothelial carcinoma (BUC) cells was much higher than that in human normal urethra epithelial cells. In order to investigate the role of HMGB1 in BUC cells, RNA interference and Talen-mediated gene knockout (KO) were used to knockdown and knockout HMGB1, respectively, in BUC cell lines BIU-87 and T24. HMGB1 knockdown/out greatly inhibited proliferation, invasion, and cell cycle G1/S transition of BUC cells. The decrease in cell viability caused by HMGB1 knockdown/out was due to an increase in apoptosis via Bax/Bcl-2, both of which were important molecules involved in the apoptotic pathway. We then investigated the effect of HMGB1 knockdown/out on the sensitivity of BUC cells treated with the anticancer drug cisplatin. Knockdown or knockout of HMGB1 rendered BUC cells more sensitive to cisplatin. The decreased expression of LC3-II and Beclin 1, which resulted in decreased levels of autophagy, could probably explain this phenomenon. Thus, HMGB1 may become a novel promising candidate for the prognosis and therapy for bladder cancer.
authors.affiliation: Department of Urology, Loudi Central Hospital of Hunan Province, Loudi, China.
authors.forename: Haiqiu
authors.initials: H
authors.lastname: Liao
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Hu
authors.forename: Yangming
authors.initials: Y
authors.lastname: Xiao
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Yin
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human