Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):650-657. doi: 10.1016/j.bbrc.2018.04.127. Epub 2018 Apr 26.
PBX1 was abnormally overexpressed and its intracellular localization was found to be frequently amplified in many types of cancer, including renal clear cell carcinoma. PBX1 displays oncogenic activity in several different types of cells, but little is known about how signaling pathways are altered, and the function of PBX1 in renal clear cell carcinoma has not been well investigated. In this study, we demonstrate that the expression of PBX1 was significantly upregulated in 30 pairs of human tissues compared to adjacent normal tissues and the overall survival rate of PBX1-high group was significantly worse than that of PBX1-low group. Furthermore, JAK2 expression is significantly correlated to PBX1 expression in human clinical specimen and PBX1 knockdown inhibits STAT3 phosphorylation and reduced transcription of STAT3 target genes Cyclin D1. More interestingly, PBX1 knockdown inhibits ccRCC cell viability, proliferation and cell cycle progression in vivo and in vitro. Thus, our results demonstrate that PBX1 plays an oncogenic role in ccRCC via JAK2/STAT3 pathway and indicate its potential application for the treatment of human ccRCC in future.
PBX1 在多种癌症中异常过表达，其细胞内定位被发现经常扩增，包括肾透明细胞癌。PBX1 在几种不同类型的细胞中表现出致癌活性，但对于信号通路如何被改变以及 PBX1 在肾透明细胞癌中的功能知之甚少。在这项研究中，我们证明与相邻正常组织相比，30 对人组织中 PBX1 的表达显著上调，且 PBX1 高表达组的总生存率明显差于 PBX1 低表达组。此外，在人类临床标本中，JAK2 表达与 PBX1 表达呈显著相关，PBX1 敲低抑制 STAT3 磷酸化并降低 STAT3 靶基因 Cyclin D1 的转录。更有趣的是，PBX1 敲低抑制 ccRCC 细胞在体内和体外的活力、增殖和细胞周期进程。因此，我们的结果表明 PBX1 通过 JAK2/STAT3 通路在 ccRCC 中发挥致癌作用，并表明其在未来治疗人类 ccRCC 中的潜在应用。
