Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells

Abstract Background Abnormal activation of the classic Wnt signaling pathway is closely related to the occurrence of epithelial cancers. B-cell lymphoma 9 (BCL9), a transcription factor, is a novel oncogene discovered in the classic Wnt pathway and promotes the occurrence and development of various...

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Main Authors: Jing Wang, Mingjun Zheng, Liancheng Zhu, Lu Deng, Xiao Li, Linging Gao, Caixia Wang, Huimin Wang, Juanjuan Liu, Bei Lin
Format: Article
Language:English
Published: BMC 2019-12-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-019-1009-5
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author Jing Wang
Mingjun Zheng
Liancheng Zhu
Lu Deng
Xiao Li
Linging Gao
Caixia Wang
Huimin Wang
Juanjuan Liu
Bei Lin
author_facet Jing Wang
Mingjun Zheng
Liancheng Zhu
Lu Deng
Xiao Li
Linging Gao
Caixia Wang
Huimin Wang
Juanjuan Liu
Bei Lin
author_sort Jing Wang
collection DOAJ
description Abstract Background Abnormal activation of the classic Wnt signaling pathway is closely related to the occurrence of epithelial cancers. B-cell lymphoma 9 (BCL9), a transcription factor, is a novel oncogene discovered in the classic Wnt pathway and promotes the occurrence and development of various tumors. Ovarian cancer is the gynecological malignant tumor with the highest mortality because it is difficult to diagnose early, and easy to relapse and metastasis. The expression and role of BCL9 in epithelial ovarian cancer (EOC) have not been studied. Thus, in this research, we aimed to investigate the expression and clinical significance of BCL9 in EOC tissues and its effect on the malignant biological behavior of human ovarian cancer cells. Methods We detect the expression of BCL9 in ovarian epithelial tumor tissues and normal ovarian tissues using immunohistochemistry and analyzed the relationship between it and clinicopathological parameters and patient prognosis. The expression of proteins was detected by Western blot. The MTT assay, flow cytometry, the scratch assay, and the transwell assay were used to detect cell proliferation, apoptosis, migration, and invasion, respectively. A total of 374 ovarian cancer tissue samples were collected using TCGA database. A gene set enrichment analysis of BCL9 was performed. Results BCL9 was overexpressed in EOC tissues. The level of BCL9 expression was correlated with the 5-year progression-free survival rate and overall survival rate in ovarian cancer patients and independently predicted the risk of ovarian cancer recurrence. Low BCL9 expression inhibited proliferation, invasion and migration of EOC cells, decreased MMP2 and MMP9 expression of ES-2 cell line, increased the BAX/BCL2 ratio and promoted apoptosis of EOC cells. Conclusion BCL9 is overexpressed in epithelial ovarian tumors, resulting in a poor prognosis for ovarian cancer patients. Low BCL9 expression can promote ovarian cancer cell apoptosis, inhibit proliferation and migration. BCL9 promotes the development of ovarian cancer.
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spelling doaj.art-af570c9158534bb59863310b6a73c1082022-12-21T22:09:34ZengBMCCancer Cell International1475-28672019-12-0119111610.1186/s12935-019-1009-5Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cellsJing Wang0Mingjun Zheng1Liancheng Zhu2Lu Deng3Xiao Li4Linging Gao5Caixia Wang6Huimin Wang7Juanjuan Liu8Bei Lin9Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityDepartment of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical UniversityAbstract Background Abnormal activation of the classic Wnt signaling pathway is closely related to the occurrence of epithelial cancers. B-cell lymphoma 9 (BCL9), a transcription factor, is a novel oncogene discovered in the classic Wnt pathway and promotes the occurrence and development of various tumors. Ovarian cancer is the gynecological malignant tumor with the highest mortality because it is difficult to diagnose early, and easy to relapse and metastasis. The expression and role of BCL9 in epithelial ovarian cancer (EOC) have not been studied. Thus, in this research, we aimed to investigate the expression and clinical significance of BCL9 in EOC tissues and its effect on the malignant biological behavior of human ovarian cancer cells. Methods We detect the expression of BCL9 in ovarian epithelial tumor tissues and normal ovarian tissues using immunohistochemistry and analyzed the relationship between it and clinicopathological parameters and patient prognosis. The expression of proteins was detected by Western blot. The MTT assay, flow cytometry, the scratch assay, and the transwell assay were used to detect cell proliferation, apoptosis, migration, and invasion, respectively. A total of 374 ovarian cancer tissue samples were collected using TCGA database. A gene set enrichment analysis of BCL9 was performed. Results BCL9 was overexpressed in EOC tissues. The level of BCL9 expression was correlated with the 5-year progression-free survival rate and overall survival rate in ovarian cancer patients and independently predicted the risk of ovarian cancer recurrence. Low BCL9 expression inhibited proliferation, invasion and migration of EOC cells, decreased MMP2 and MMP9 expression of ES-2 cell line, increased the BAX/BCL2 ratio and promoted apoptosis of EOC cells. Conclusion BCL9 is overexpressed in epithelial ovarian tumors, resulting in a poor prognosis for ovarian cancer patients. Low BCL9 expression can promote ovarian cancer cell apoptosis, inhibit proliferation and migration. BCL9 promotes the development of ovarian cancer.https://doi.org/10.1186/s12935-019-1009-5Ovarian cancerBCL9Malignant biological behaviorTargeted therapy
spellingShingle Jing Wang
Mingjun Zheng
Liancheng Zhu
Lu Deng
Xiao Li
Linging Gao
Caixia Wang
Huimin Wang
Juanjuan Liu
Bei Lin
Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
Cancer Cell International
Ovarian cancer
BCL9
Malignant biological behavior
Targeted therapy
title Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
title_full Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
title_fullStr Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
title_full_unstemmed Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
title_short Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
title_sort low bcl9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation migration and increasing apoptosis to cancer cells
topic Ovarian cancer
BCL9
Malignant biological behavior
Targeted therapy
url https://doi.org/10.1186/s12935-019-1009-5
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