HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Abstract

Background: Homeobox B4 (HOXB4) is associated with the poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains to be determined. Methods：The Cancer Genome Atlas (TCGA) database indicated that high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed through a colony formation, migration, and invasion assay. The effect of HOXB4 on the expression of EMT and cancer stem cell markers was detected. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was performed in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results：Results showed that the expression of HOXB4 was higher in OV tissues than in normal tissues and correlated with the poor prognosis of OV. HOXB4 knockdown suppressed the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the up-regulation of HOXB4 in OV cells. The binding of two DNA motifs through HOXB4 regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in promoting tumor proliferation and metastasis was verified in mice. Further investigation revealed that HOXB4 triggered Snail and Zeb1 expression. Conclusion: Overall, HOXB4 overexpression was remarkably correlated with the poor prognosis of OV. HOXB4 up-regulated DHDDS, which co-contributed to the enhancer proliferation and invasion of OV cells, thus accelerating the malignant progression of OV.

The regulatory role of HOX interacting lncRNA in oral cancer—An in silico analysis

“…For example, upregulated HOXD10 and downregulated HOXB4 were not found in Stage III of oral cancer. These could be important genes that are involved in bringing about the shift of cells from a non‐metastatic state to a metastatic state 45,46 . Their interaction with lncRNAs could be a reason for their absence in a particular stage and the mechanism by which they bring about an epithelial‐mesenchymal transition in oral cancer is still unclear 47 …”

“…These could be important genes that are involved in bringing about the shift of cells from a non-metastatic state to a metastatic state. 45,46 Their interaction with lncRNAs could be a reason for their absence in a particular stage and the mechanism by which they bring about an epithelial-mesenchymal transition in oral cancer is still unclear. 47 Understanding the drug-lncRNA interaction has led to the development of better therapeutic approaches in cancer.…”