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鉴定线粒体转录因子 A 作为前列腺癌发生和预后的潜在生物标志物。

Identifying Mitochondrial Transcription Factor A As a Potential Biomarker for the Carcinogenesis and Prognosis of Prostate Cancer.

机构信息

The Third Central Hospital of Tianjin, Tianjin, China.

Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.

出版信息

Genet Test Mol Biomarkers. 2023 Jan;27(1):5-11. doi: 10.1089/gtmb.2022.0141.

DOI:10.1089/gtmb.2022.0141
PMID:36719981
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9902047/
Abstract

Mitochondrial functional transformation contributes to the carcinogenesis of the prostate by meeting the metabolic needs of cancer cells. Mitochondrial transcription factor A (TFAM) is a pivotal regulator that maintains homeostasis of mitochondrial function. However, its role in prostate carcinogenesis has not been well elucidated. In the present study, we analyzed the expression of in normal prostate tissue and prostate cancer using public databases; a prostate-tissue chip was used to verify the results. The expression of TFAM in normal cells and in prostate cancer cells was determined by western blotting analysis. We knocked down TFAM in the prostate cancer cell line PC3 using a specific shRNA to explore the potential effects of TFAM in prostatic carcinogenesis. We observed higher expression levels of TFAM in prostate cancer tissue than in normal prostate tissue and tumor adjacent normal tissues. A receiver operating characteristic curve was drawn that demonstrated the diagnostic efficacy of using expression for prostate cancer prognoses. Elevated levels of may indicate poorer overall survival in prostate cancer patients. Western blotting assays also showed that relative to the normal prostatic epithelial cell line RWPE-1, prostate cancer cell lines PC3 and DU145 expressed more TFAM protein. Furthermore, knockdown of TFAM inhibited the colony-formation capability of PC3 cells. Collectively, these results suggest that TFAM promotes carcinogenesis of the prostate, and may constitute a marker to be used in the diagnosis and prognosis of prostate cancer.

摘要

线粒体功能转化通过满足癌细胞的代谢需求促进前列腺癌的发生。线粒体转录因子 A(TFAM)是维持线粒体功能稳态的关键调节因子。然而,其在前列腺癌发生中的作用尚未得到充分阐明。在本研究中,我们使用公共数据库分析了在正常前列腺组织和前列腺癌中 的表达;使用前列腺组织芯片验证了结果。通过 Western blot 分析确定了 TFAM 在正常细胞和前列腺癌细胞中的表达。我们使用特异性 shRNA 敲低前列腺癌细胞系 PC3 中的 TFAM,以探讨 TFAM 在前列腺癌发生中的潜在作用。我们观察到前列腺癌组织中 TFAM 的表达水平高于正常前列腺组织和肿瘤旁正常组织。绘制了受试者工作特征曲线,证明了 使用 表达进行前列腺癌预后诊断的功效。水平升高可能表明前列腺癌患者的总体生存率较差。Western blot 分析还显示,与正常前列腺上皮细胞系 RWPE-1 相比,前列腺癌细胞系 PC3 和 DU145 表达更多的 TFAM 蛋白。此外,TFAM 的敲低抑制了 PC3 细胞的集落形成能力。综上所述,这些结果表明 TFAM 促进了前列腺的癌变,可能成为前列腺癌诊断和预后的标志物。

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Targeting Mitochondrial Metabolism in Prostate Cancer with Triterpenoids.用三萜类化合物靶向前列腺癌中的线粒体代谢。
Int J Mol Sci. 2021 Feb 28;22(5):2466. doi: 10.3390/ijms22052466.
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020:全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
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Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance.线粒体 ROS 通过破坏 TFAM 介导的 mtDNA 维持来促进缺血性急性肾损伤中的线粒体功能障碍和炎症。
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ATM inhibition enhances cancer immunotherapy by promoting mtDNA leakage and cGAS/STING activation.ATM 抑制通过促进 mtDNA 泄漏和 cGAS/STING 激活增强癌症免疫治疗。
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Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death.线粒体 DNA 应激引发自噬依赖性铁死亡。
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