Li Minghui, Cai Yong, Zhao Hongmei, Xu Zongyuan, Sun Qingsong, Luo Man, Gu Lizhi, Meng Min, Han Xiang, Sun Hong
Department of Emergency Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Tumour Biol. 2015 Jun;36(6):4785-92. doi: 10.1007/s13277-015-3130-y. Epub 2015 Feb 3.
Human urinary bladder cancer (UBC) is the fourth most common cancer and the eighth most common cause of cancer death in the USA. High mobility group box 3 (HMGB3), a member of a family of proteins containing one or more high mobility group DNA binding motifs, was reported to be overexpressed in a variety of human cancers. However, the expression and role of HMGB3 in human UBC remains unclear. Here, we found that UBC patients had upregulated HMGB at both mRNA and protein levels. Immunochemistry (IHC) evaluation of HMGB3 expression in 113 UBC clinical specimens showed that high expression of HMGB3 had positive correlation with UBC tumor size (P = 0.019), tumor WHO grade (P = 0.031), stage (P = 0.028), and lymph node metastasis (P = 0.017). Moreover, patients with higher HMGB3 expression showed a poorer overall survival rate than those with relatively low HMGB3 (P = 0.0079, log-rank test). Multivariate analysis revealed that HMGB3 expression is an independent prognostic marker. The UBC cancer cell proliferation and migration ability were measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and wound healing assays, respectively. RNA interference of HMGB3 in UBC cell lines inhibited cancer cell growth and migration, along with the downregulation of PCNA and MMP2 protein levels. In sum, our data suggests HMGB3 may serve as an important oncoprotein and indicate that overexpression of HMGB3 in UBC could be used as a potential prognostic marker.
人类膀胱癌（UBC）是美国第四大常见癌症，也是癌症死亡的第八大常见原因。高迁移率族蛋白盒3（HMGB3）是一种包含一个或多个高迁移率族DNA结合基序的蛋白质家族成员，据报道在多种人类癌症中过表达。然而，HMGB3在人类UBC中的表达和作用仍不清楚。在此，我们发现UBC患者在mRNA和蛋白质水平上均上调了HMGB。对113份UBC临床标本中HMGB3表达的免疫化学（IHC）评估显示，HMGB3的高表达与UBC肿瘤大小（P = 0.019）、肿瘤WHO分级（P = 0.031）、分期（P = 0.028）和淋巴结转移（P = 0.017）呈正相关。此外，HMGB3表达较高的患者总体生存率低于HMGB3相对较低的患者（P = 0.0079，对数秩检验）。多变量分析显示，HMGB3表达是一个独立的预后标志物。分别通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）和伤口愈合试验测量UBC癌细胞的增殖和迁移能力。在UBC细胞系中对HMGB3进行RNA干扰可抑制癌细胞生长和迁移，同时下调PCNA和MMP2蛋白水平。总之，我们的数据表明HMGB3可能是一种重要的癌蛋白，并表明UBC中HMGB3的过表达可作为一种潜在的预后标志物。
