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.

The progression of HMGB1-induced autophagy in cancer biology

“…Radiation therapy can preserve urinary and sexual function and predict a high quality of life in patients 104. Liao et al105 showed that a decreased level of HMGB1-induced autophagy in bladder urothelial carcinoma (BUC) cells significantly inhibited the viability of BUC cells. Shrivastava et al106 reported the important role of HMGB1 as a predictive marker in bladder cancers subjected to radiation therapy and its correlation with autophagy.…”

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

“…HMGB1 also functions as an inducer of EMT in human cancer cells (27)(28)(29)(30)(31). HMGB1 expression was much higher in bladder cancer cells than normal urethra epithelial cells and was associated with cell invasion (32,33). However, the mechanism of HMGB1 in bladder cancer is largely unknown.…”

Antiproliferative Activity and Induction of Apoptosis in Human Melanoma Cells by Houttuynia cordata Thunb Extract

“…Increased expression of HMGB1 is correlated with progression of human cutaneous melanoma and poor patient survival (21). Knockdown or knockout of HMGB1 greatly inhibited proliferation, invasion, and cell cycle G 1 /S transition of bladder urothelial carcinoma cells (22). The aim of this study was to elucidate the potential roles of caspase-3 and caspase-8 in HCT-mediated apoptosis and to dissect the mechanisms that regulate HMGB1 release in a malignant melanoma cell line.…”