Abstract
BackgroundAbnormal 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.MethodsWe 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.ResultsBCL9 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.ConclusionBCL9 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.
Highlights
Abnormal activation of the classic Wnt signaling pathway is closely related to the occurrence of epithelial cancers
B-cell lymphoma 9 (BCL9) was significantly upregulated in ovarian cancer The immunohistochemistry results showed that BCL9 was mainly located in the nucleus in ovarian epithelial tumors and partly in the cytoplasm
High BCL9 expression was associated with a poor prognosis in ovarian cancer patients We found that the level of BCL9 expression, Federation International of Gynecology and Obstetrics (FIGO) stage, Table 1 Expression of BCL9 antigen in different ovarian tissues
Summary
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. BCL9 can form a complex with stable β-catenin, pygopus family coactivator, and T cell factor transcriptional cofactor (TCF)/lymphocyte enhancer (LEF), mainly in the nucleus This complex activates transcription and expression by binding to the promoters of many target genes [3, 5,6,7,8,9]. The present study explored the expression of BCL9 in human ovarian epithelial tumors and its relationship to clinicopathological parameters and changes in the malignant biological behavior of human ovarian cancer cells. We sought to provide a theoretical basis for further investigations of the occurrence and development of ovarian cancer and the search for new therapeutic targets
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