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miR-27 异构体的表达、功能和进化分析及其在代谢过程中的响应。

Analysis of the expression, function, and evolution of miR-27 isoforms and their responses in metabolic processes.

机构信息

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing 210023, China.

Department of Bioinformatics, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

出版信息

Genomics. 2019 Dec;111(6):1249-1257. doi: 10.1016/j.ygeno.2018.08.004. Epub 2018 Aug 23.

Abstract

This study aimed to discuss the potential roles of isomiRs of miR-27 family in metabolisms associated with disease via analyses of their evolution, expression, and function. miR-27b-3p was relatively highly expressed in liver cancer samples compared to miR-27a-3p and miR-27-5p loci. The diversity of isomiRs in miR-27-3p locus is similar to that of miRNAs among homologous genes. IsomiRs exhibited variable expression across different cancer tissue types, and some of them were abnormally expressed in ob/ob mice. Further experimental validation indicated that the protein expression of metabolism-related proteins, including PEPCK, G6Pase, FAS, and CPT1A, were significantly suppressed when canonical miR-27b was transfected into AML-12 cells. In contrast, the expression of these proteins was only slightly inhibited by isomiR-27b-1 or isomiR-27b-2 after transfection into AML-12 cells. These observations support that isomiRs exhibiting sequence divergence are functional regulatory molecules, and that they may contribute to biological processes via coordinated interactions in regulatory networks.

摘要

本研究旨在通过分析 miR-27 家族的 isomiRs 的进化、表达和功能,探讨其在与疾病相关的代谢中的潜在作用。与 miR-27a-3p 和 miR-27-5p 基因座相比,miR-27b-3p 在肝癌样本中相对高表达。miR-27-3p 基因座的 isomiRs 多样性与同源基因中的 miRNAs 相似。isomiRs 在不同的癌症组织类型中表现出不同的表达,其中一些在 ob/ob 小鼠中异常表达。进一步的实验验证表明,当将经典的 miR-27b 转染到 AML-12 细胞中时,与代谢相关的蛋白质(包括 PEPCK、G6Pase、FAS 和 CPT1A)的蛋白表达显著受到抑制。相比之下,当将 isomiR-27b-1 或 isomiR-27b-2 转染到 AML-12 细胞中时,这些蛋白质的表达仅受到轻微抑制。这些观察结果支持具有序列差异的 isomiRs 是功能调节分子,并且它们可能通过在调控网络中的协调相互作用来促进生物过程。

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