{"title":"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。","authors":"Jianbin Chen, Tairen Wang, Weina Mu","doi":"10.1089/gtmb.2023.0641","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Objective:</i></b> 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. <b><i>Materials and Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A C->T Variation in 3'-Untranslated Region Elevates MED12 Protein Level in Breast Cancer That Relates to Better Prognosis.\",\"authors\":\"Jianbin Chen, Tairen Wang, Weina Mu\",\"doi\":\"10.1089/gtmb.2023.0641\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Objective:</i></b> 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. <b><i>Materials and Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.</p>\",\"PeriodicalId\":12603,\"journal\":{\"name\":\"Genetic testing and molecular biomarkers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic testing and molecular biomarkers\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/gtmb.2023.0641\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2023.0641","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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