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

Jing Wang; Mingjun Zheng; Liancheng Zhu; Lu Deng; Xiao Li; Linging Gao; Caixia Wang; Huimin Wang; Juanjuan Liu; Bei Lin

doi:10.1186/s12935-019-1009-5

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

Cancer Cell Int. 2019 Dec 6:19:330. doi: 10.1186/s12935-019-1009-5. eCollection 2019.

Authors

Jing Wang^{1

2}, Mingjun Zheng^{1

2}, Liancheng Zhu^{1

2}, Lu Deng^{1

2

3}, Xiao Li^{1

2}, Linging Gao^{1

2}, Caixia Wang^{1

2}, Huimin Wang^{1

2

4}, Juanjuan Liu^{1

2}, Bei Lin^{1

2}

Affiliations

¹ 1Department of Obstetrics and Gynaecology, Shengjing Hospital Affiliated to China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004 Liaoning China.
² Key Laboratory of Maternal-Fetal Medicine of Liaoning Province and, Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, No. 7 Mulan Road, Xihu District, Benxi, 117000 Liaoning China.
³ 3Obstetrics and Gynaecology Hospital of Fudan Universuty, Shanghai, China.
⁴ 4Department of Gynecology, Liaoning Cancer Hospital & Institute China Medical University, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110000 Liaoning China.

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.

Keywords: BCL9; Malignant biological behavior; Ovarian cancer; Targeted therapy.