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HOXB4 通过 DHDDS 促进卵巢癌的恶性进展。

HOXB4 promotes the malignant progression of ovarian cancer via DHDDS.

机构信息

Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Key Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China.

出版信息

BMC Cancer. 2020 Mar 16;20(1):222. doi: 10.1186/s12885-020-06725-4.

DOI:10.1186/s12885-020-06725-4
PMID:32178630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7077141/
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.

摘要

背景

同源盒 B4（HOXB4）与多种癌症类型的不良预后相关。然而，HOXB4 如何促进卵巢癌（OV）的进展尚不清楚。

方法

癌症基因组图谱（TCGA）数据库表明，OV 中 HOXB4 水平较高与预后不良相关。通过集落形成、迁移和侵袭实验证实了 HOXB4 的生物学功能。确定 HOXB4 对 EMT 细胞标志物表达的影响。通过 ChIP 实验检测 HOXB4 的转录靶标 DHDDS。在裸鼠中生成异种移植肿瘤模型，以检测 HOXB4 在肿瘤增殖和转移中的作用。

结果

结果表明，HOXB4 蛋白水平在 OV 组织中高于正常组织，与 OV 的不良预后相关。HOXB4 减少抑制了 OV 细胞在体外的增殖和侵袭能力。相反，HOXB4 在 OV 细胞中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，有助于 OV 的恶性进展。在小鼠中验证了 HOXB4 在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 的表达。

结论

总体而言，OV 中 HOXB4 的过表达与不良预后显著相关。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/60dbade434e9/12885_2020_6725_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/32417587ad79/12885_2020_6725_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/7520d909277f/12885_2020_6725_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/025455b9df4e/12885_2020_6725_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/99f9ffec67d0/12885_2020_6725_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/f7a061dd53f0/12885_2020_6725_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/60dbade434e9/12885_2020_6725_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/32417587ad79/12885_2020_6725_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/7520d909277f/12885_2020_6725_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/025455b9df4e/12885_2020_6725_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/99f9ffec67d0/12885_2020_6725_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/f7a061dd53f0/12885_2020_6725_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf77/7077141/60dbade434e9/12885_2020_6725_Fig6_HTML.jpg

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