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BAIAP2L2通过血管内皮生长因子(VEGF)和凋亡信号通路促进前列腺癌(PCa)的恶性发展。

BAIAP2L2 facilitates the malignancy of prostate cancer (PCa) via VEGF and apoptosis signaling pathways.

作者信息

Song Yuanzi, Zhuang Guishan, Li Jiazhen, Zhang Mingqing

机构信息

Department of Urology, Zibo First Hospital, Emeishan East Road, Zibo, China.

Department of Urology, Weifang People's Hospital, 151 Guangwen Street, Kuiwen District, Weifang, 261041, Shandong, China.

出版信息

Genes Genomics. 2021 Apr;43(4):421-432. doi: 10.1007/s13258-021-01061-8. Epub 2021 Mar 1.

DOI:10.1007/s13258-021-01061-8
PMID:33646530
Abstract

BACKGROUND

Prostate cancer (PCa) is the second most common type of male cancer in western. Despite key roles of brain-specific angiogenesis inhibitor 1-associated protein like 2 (BAIAP2L2) in several cancers, the function of BAIAP2L2 in PCa is never reported.

OBJECTIVE

We aimed to investigate the role of BAIAP2L2 in the progression of PCa and decipher the underlying mechanisms.

METHODS

RNA sequencing data from TCGA database were used to evaluate the expression of BAIAP2L2 in PCa. Survival analysis and Cox regression model analysis were conducted to evaluate the prognostic value of BAIAP2L2. BAIAP2L2-associated pathways were preliminary analyzed by Gene Set Enrichment Analysis (GSEA) method and confirmed by western blot assays. Cell proliferation and transwell assays were performed to determine biological behaviors in BAIAP2L2 knocked-down or overexpressed PCa cell lines including LNCaP and PC-3 cells.

RESULTS

In our study, BAIAP2L2 was significantly up-regulated in PCa tissues and cell lines and independently associated with the poor prognosis of PCa patients. Knockdown of BAIAP2L2 notably repressed proliferation, migration and invasion of PCa cells. And overexpression of BAIAP2L2 obtained the contrary results. Mechanically, GSEA method and western blot results of key molecules in signaling pathways implicated that the depletion of BAIAP2L2 inactivated the vascular endothelial growth factors (VEGFs) and induced apoptosis signaling pathways in PCa cells.

CONCLUSIONS

Overall, these findings revealed that BAIAP2L2 may support tumorigenesis and malignant development of prostate cancer cells via VEGF and apoptosis signaling pathways, and it could be considered as a promising biomarker and independent prognostic predictor of prostate cancer.

摘要

背景

前列腺癌(PCa)是西方男性中第二常见的癌症类型。尽管脑特异性血管生成抑制因子1相关蛋白样2(BAIAP2L2)在多种癌症中发挥关键作用,但BAIAP2L2在PCa中的功能尚未见报道。

目的

我们旨在研究BAIAP2L2在PCa进展中的作用,并阐明其潜在机制。

方法

利用来自TCGA数据库的RNA测序数据评估BAIAP2L2在PCa中的表达。进行生存分析和Cox回归模型分析以评估BAIAP2L2的预后价值。通过基因集富集分析(GSEA)方法初步分析BAIAP2L2相关通路,并通过蛋白质免疫印迹分析进行验证。进行细胞增殖和Transwell分析以确定BAIAP2L2敲低或过表达的PCa细胞系(包括LNCaP和PC-3细胞)中的生物学行为。

结果

在我们的研究中,BAIAP2L2在PCa组织和细胞系中显著上调,并且与PCa患者的不良预后独立相关。敲低BAIAP2L2可显著抑制PCa细胞的增殖、迁移和侵袭。而BAIAP2L2的过表达则得到相反的结果。机制上,GSEA方法和信号通路中关键分子的蛋白质免疫印迹结果表明,BAIAP2L2的缺失使血管内皮生长因子(VEGFs)失活,并诱导PCa细胞中的凋亡信号通路。

结论

总体而言,这些发现表明BAIAP2L2可能通过VEGF和凋亡信号通路支持前列腺癌细胞的肿瘤发生和恶性发展,并且它可被视为前列腺癌有前景的生物标志物和独立的预后预测指标。

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