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SPC25的上调促进乳腺癌。

Up-regulation of SPC25 promotes breast cancer.

作者信息

Wang Qian, Zhu Yanhui, Li Zhouxiao, Bu Qian, Sun Tong, Wang Hanjin, Sun Handong, Cao Xiufeng

机构信息

Department of Oncology Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Aging (Albany NY). 2019 Aug 10;11(15):5689-5704. doi: 10.18632/aging.102153.

Abstract

In this study, expression of the SPC25 gene was characterized in breast cancer (BC), and its effects on BC development and progression, functions in BC cells, and potential underlying mechanisms were examined. Data from TCGAportal and FIREBROWSE indicated that SPC25 was upregulated in BC tissues compared to normal tissues, and CANCERTOOL indicated that higher SPC25 mRNA levels were associated with increased probability of recurrence and poorer survival in BC patients. BC patients with higher SPC25 expression displayed shorter distant metastasis-free survival, relapse-free survival, and overall survival. Colony formation and CCK-8 experiments confirmed that SPC25 promoted proliferation of BC cells. Single-cell analysis indicated that SPC25 is associated with cell cycle regulation, DNA damage and repair, and BC cell proliferation. SPC25 knockdown suppressed proliferation of BC cells. MiRNAs, circRNAs, RNA-binding proteins, transcription factors, and immune factors that might interact with SPC25 mRNA to promote BC were also identified. These findings suggest that SPC25 levels are higher in more malignant BC subtypes and are associated with poor prognosis in BC patients. In addition, DNA methyltransferase inhibitor and transcription factors inhibitor treatments targeting SPC25 might improve survival in BC patients.

摘要

在本研究中,对乳腺癌(BC)中SPC25基因的表达进行了表征,并研究了其对BC发生发展的影响、在BC细胞中的功能以及潜在的作用机制。来自TCGAportal和FIREBROWSE的数据表明,与正常组织相比,BC组织中SPC25表达上调,而CANCERTOOL表明,较高的SPC25 mRNA水平与BC患者复发概率增加和生存率降低相关。SPC25表达较高的BC患者无远处转移生存期、无复发生存期和总生存期较短。集落形成实验和CCK-8实验证实SPC25促进BC细胞增殖。单细胞分析表明,SPC25与细胞周期调控、DNA损伤与修复以及BC细胞增殖有关。敲低SPC25可抑制BC细胞增殖。还鉴定了可能与SPC25 mRNA相互作用以促进BC的微小RNA、环状RNA、RNA结合蛋白、转录因子和免疫因子。这些发现表明,在恶性程度更高的BC亚型中SPC25水平更高,且与BC患者的不良预后相关。此外,针对SPC25的DNA甲基转移酶抑制剂和转录因子抑制剂治疗可能会改善BC患者的生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4345/6710047/22d3d585b826/aging-11-102153-g001.jpg

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