Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed by colony formation, migration, and invasion assays. The effect of HOXB4 on the expression of EMT cell markers was determined. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was generated in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. The results showed that HOXB4 protein levels were higher in OV tissues than in normal tissues and correlated with poor prognosis of OV. HOXB4 reduction inhibited the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the upregulation of HOXB4 in OV cells. The binding of HOXB4 to two DNA motifs regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in contributing to tumor development in vivo was verified in mice. Further results indicated that HOXB4 induced Snail and Zeb1 expression. Overall, HOXB4 overexpression was remarkably correlated with poor prognosis of OV. Mechanistically, HOXB4 enhances the proliferation and invasion of tumor cells by activating DHDDS, thereby promoting the malignant progression of OV.

中文翻译：

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HOXB4通过DHDDS促进卵巢癌的恶性进展

同源盒B4（HOXB4）与各种癌症类型的不良预后相关。但是，HOXB4如何促进卵巢癌（OV）进展尚不清楚。癌症基因组图谱（TCGA）数据库表明，OV中高水平的HOXB4与不良预后相关。HOXB4的生物学功能已通过菌落形成，迁移和侵袭试验得以证实。确定了HOXB4对EMT细胞标志物表达的影响。HOXB4的转录靶是DHDDS，其通过ChIP测定法检测。在裸鼠中产生异种移植肿瘤模型，以检测HOXB4在肿瘤增殖和转移中的作用。结果显示，OVX组织中HOXB4蛋白水平高于正常组织，并且与OV的预后不良相关。HOXB4的减少抑制了OV细胞的体外增殖和侵袭能力。相反，OV细胞中HOXB4的上调增强了这些作用。HOXB4与两个DNA基序的结合调节DHDDS的表达并有助于OV的恶性进展。在小鼠中证实了HOXB4在体内促进肿瘤发展中的作用。进一步的结果表明HOXB4诱导了Snail和Zeb1表达。总体而言，HOXB4过表达与OV的不良预后显着相关。从机制上讲，HOXB4通过激活DHDDS增强肿瘤细胞的增殖和侵袭，从而促进OV的恶性进展。HOXB4与两个DNA基序的结合调节DHDDS的表达并有助于OV的恶性进展。在小鼠中证实了HOXB4在体内促进肿瘤发展中的作用。进一步的结果表明HOXB4诱导了Snail和Zeb1表达。总体而言，HOXB4过表达与OV的不良预后显着相关。从机制上讲，HOXB4通过激活DHDDS增强肿瘤细胞的增殖和侵袭，从而促进OV的恶性进展。HOXB4与两个DNA基序的结合调节DHDDS的表达并有助于OV的恶性进展。在小鼠中证实了HOXB4在体内促进肿瘤发展中的作用。进一步的结果表明HOXB4诱导了Snail和Zeb1表达。总体而言，HOXB4过表达与OV的不良预后显着相关。从机制上讲，HOXB4通过激活DHDDS增强肿瘤细胞的增殖和侵袭，从而促进OV的恶性进展。