3'-Untranslated 区域的 C->T 变异可提高乳腺癌患者的 MED12 蛋白水平,从而改善预后。

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY
Genetic testing and molecular biomarkers Pub Date : 2024-09-01 Epub Date: 2024-08-21 DOI:10.1089/gtmb.2023.0641
Jianbin Chen, Tairen Wang, Weina Mu
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引用次数: 0

摘要

目的介导复合体亚基 12(MED12)是各类人类癌症中最常见的突变基因之一。然而,人们对 MED12 在乳腺癌患者中的作用仍缺乏了解。因此,本研究旨在探讨 MED12 在乳腺癌中的作用。材料与方法:我们利用 UALCAN 平台(http://ualcan.path.uab.edu/)分析了 MED12 的转录表达、蛋白表达和蛋白磷酸化数据。我们的研究涉及 35 例乳腺癌患者。我们从这些样本中提取了蛋白质和 RNA。为了获得 MED12 3'-UTR 的序列,我们进行了反转录聚合酶链反应和测序。然后,我们利用 TargetScan 预测了 MED12 3'-UTR 的 miRNA 靶点,并通过双荧光素酶试验证实了 miRNA 与 MED12 3'-UTR 之间的相互作用。结果显示在乳腺癌中,MED12的蛋白水平上调,而mRNA水平没有明显变化。有趣的是,较高水平的 MED12 mRNA 与较好的预后相关,而 MED12 蛋白水平升高的患者预后往往较差。此外,通过对 MED12 3'-UTR 序列的分析,我们发现了乳腺肿瘤特有的 C->T 变异。我们还发现了四个直接靶向 MED12 3'-UTR 的 miRNA(miR-204、-211、-450 b 和 -518a)。最重要的是,这种 C->T 变异破坏了 MED12 3'-UTR 与 miR-450b 之间的相互作用,最终导致乳腺癌中 MED12 的上调。结论我们的研究揭示了一个重要发现,即 MED12 3'-UTR 中的一个突变位点导致了 MED12 在乳腺癌中的上调。这一突变破坏了特定 miRNA 与 MED12 mRNA 之间的相互作用,导致 MED12 的表达增加。这些发现对乳腺癌诊断具有重要意义,因为该突变位点可作为一种有效的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A C->T Variation in 3'-Untranslated Region Elevates MED12 Protein Level in Breast Cancer That Relates to Better Prognosis.

Objective: Mediator complex subunit 12 (MED12) is among the most frequently mutated genes in various types of human cancers. However, there is still a lack of understanding regarding the role of MED12 in breast cancer patient. Therefore, the aim of this study is to explore the roles of MED12 in breast cancer. Materials and Methods: We utilized the UALCAN platform (http://ualcan.path.uab.edu/) for analyzing the transcriptional expression, protein expression, and protein phosphorylation data of MED12. Our study involved 35 breast cancer patients. From these samples, we extracted proteins and RNA. To obtain the sequence of MED12 3'-UTR, we performed reverse transcription-polymerase chain reaction and sequencing. We then used TargetScan to predict the miRNA targets of MED12 3'-UTR and confirmed the interactions between miRNAs and MED12 3'-UTR through dual luciferase assay. Results: The protein level of MED12 was upregulated in breast cancer, while the mRNA level did not show significant changes. Interestingly, higher levels of MED12 mRNA were associated with better prognosis, whereas patients with increased MED12 protein levels tended to have a poorer prognosis. Furthermore, through our analysis of the MED12 3'-UTR sequence, we identified a specific C->T variation that was unique to breast tumors. We also identified four miRNAs (miR-204, -211, -450 b, and -518a) that directly target MED12 3'-UTR. Most important, this C->T variation disrupts the interaction between MED12 3'-UTR and miR-450b, ultimately leading to the upregulation of MED12 in breast cancer. Conclusion: Our study revealed a significant finding regarding a mutation site in the MED12 3'-UTR that contributes to the upregulation of MED12 in breast cancer. This mutation disrupts the interactions between specific miRNAs and MED12 mRNA, leading to increased expression of MED12. These findings have important implications for breast cancer diagnosis, as this mutation site can serve as a potent biomarker.

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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
63
审稿时长
1 months
期刊介绍: Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results. Genetic Testing and Molecular Biomarkers coverage includes: -Diagnosis across the life span- Risk assessment- Carrier detection in individuals, couples, and populations- Novel methods and new instrumentation for genetic testing- Results of molecular, biochemical, and cytogenetic testing- Genetic counseling
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