HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

Abstract Background Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods The Cancer Genome Atlas (TCGA) database indicated that a high level of HOXB4 in OV was correlated with poor prognosi...

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Main Authors: Na Li, Jin-hai Gou, Jiao Xiong, Juan-juan You, Zheng-yu Li
Format: Article
Language:English
Published: BMC 2020-03-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-020-06725-4
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author Na Li
Jin-hai Gou
Jiao Xiong
Juan-juan You
Zheng-yu Li
author_facet Na Li
Jin-hai Gou
Jiao Xiong
Juan-juan You
Zheng-yu Li
author_sort Na Li
collection DOAJ
description Abstract Background Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods 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. Results 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. Conclusion 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.
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spelling doaj.art-406b734b8d504a8e843402fec5a3b3442022-12-21T23:47:58ZengBMCBMC Cancer1471-24072020-03-0120111210.1186/s12885-020-06725-4HOXB4 promotes the malignant progression of ovarian cancer via DHDDSNa Li0Jin-hai Gou1Jiao Xiong2Juan-juan You3Zheng-yu Li4Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityDepartment of Obstetrics and Gynecology, The first affiliated Hospital of Zunyi Medical UniversityDepartment of Obstetrics and Gynecology, The first affiliated Hospital of Zunyi Medical UniversityDepartment of Gynecology and Obstetrics, West China Second University Hospital, Sichuan UniversityAbstract Background Homeobox B4 (HOXB4) is correlated with poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains unclear. Methods 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. Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12885-020-06725-4Ovarian cancerHomeobox B4Malignant progressionDHDDS
spellingShingle Na Li
Jin-hai Gou
Jiao Xiong
Juan-juan You
Zheng-yu Li
HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
BMC Cancer
Ovarian cancer
Homeobox B4
Malignant progression
DHDDS
title HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
title_full HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
title_fullStr HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
title_full_unstemmed HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
title_short HOXB4 promotes the malignant progression of ovarian cancer via DHDDS
title_sort hoxb4 promotes the malignant progression of ovarian cancer via dhdds
topic Ovarian cancer
Homeobox B4
Malignant progression
DHDDS
url http://link.springer.com/article/10.1186/s12885-020-06725-4
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