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

Low BCL9 expression inhibited ovarian epithelial malignant tumor progression by decreasing proliferation, migration, and increasing apoptosis to cancer cells
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低 BCL9 表达通过减少癌细胞的增殖、迁移和增加凋亡来抑制卵巢上皮恶性肿瘤的进展

DOI:
10.1186/s12935-019-1009-5
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发表时间:
2019-12
影响因子:
5.8
通讯作者:
Lin Bei
Lin Bei
中科院分区:
医学2区
文献类型:
--
作者:
Wang Jing;Zheng Mingjun;Zhu Liancheng;Deng Lu;Li Xiao;Gao Linging;Wang Caixia;Wang Huimin;Liu Juanjuan;Lin Bei

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研究背景经典Wnt信号通路的异常激活与上皮性癌的发生密切相关。 B细胞淋巴瘤9(BCL9)是一种转录因子,是经典Wnt通路中发现的新型癌基因,促进多种肿瘤的发生和发展。卵巢癌由于早期诊断困难、易复发、转移,是死亡率最高的妇科恶性肿瘤。尚未研究 BCL9 在上皮性卵巢癌 (EOC) 中的表达和作用。因此,本研究旨在探讨BCL9在EOC组织中的表达情况、临床意义及其对人卵巢癌细胞恶性生物学行为的影响。方法采用免疫组化方法检测卵巢上皮性肿瘤组织和正常卵巢组织中BCL9的表达,分析其与临床病理参数及患者预后的关系。通过Western blot检测蛋白表达。 MTT法、流式细胞仪、划痕法和transwell法分别检测细胞增殖、凋亡、迁移和侵袭。利用TCGA数据库共收集374份卵巢癌组织样本。对BCL9进行基因集富集分析。结果BCL9在EOC组织中过表达。 BCL9表达水平与卵巢癌患者的5年无进展生存率和总生存率相关,并独立预测卵巢癌复发的风险。 BCL9低表达抑制EOC细胞增殖、侵袭和迁移,降低ES-2细胞系MMP2和MMP9表达,升高BAX/BCL2比值,促进EOC细胞凋亡。结论BCL9在上皮性卵巢肿瘤中过度表达,导致卵巢癌患者预后不良。 BCL9低表达可促进卵巢癌细胞凋亡、抑制增殖和迁移。 BCL9 促进卵巢癌的发展。
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.
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