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竞争性内源性RNA网络及其治疗意义:疾病研究的新视野

Competing endogenous RNAs network and therapeutic implications: New horizons in disease research.

作者信息

El-Ashmawy Nahla E, Khedr Eman G, Darwish Renad T, Ibrahim Amera O

机构信息

Biochemistry Department, Faculty of Pharmacy, Tanta University, 31527, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, El Sherouk City, Cairo 11837, Egypt.

Biochemistry Department, Faculty of Pharmacy, Tanta University, 31527, Egypt.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2025 Mar;1868(1):195073. doi: 10.1016/j.bbagrm.2024.195073. Epub 2024 Dec 2.

Abstract

Different diseases may arise from the dysregulation of non-coding RNAs (ncRNAs), which regulation is necessary for maintaining cellular homeostasis. ncRNAs are regulated by transcriptional, post-transcriptional, translational and post-translational processes. Post-transcriptional regulation of gene expression is carried out by microRNAs (miRNAs), a class of small ncRNA molecules, which can identify their target sites by a brief nucleotide sequence, known as the miRNA response element (MRE), present on the miRNA seed sequence and the target transcript. This binding between miRNAs and targets can regulate the gene expression through inhibition of translation or degradation of target messenger RNA (mRNA). The transcripts that share MREs can be involved in competition for the central miRNA pool, which could have an indirect impact on each other's regulation. This competition network is called competing endogenous RNAs network (ceRNET). Many ncRNAs, including circular RNA, pseudogene, and long non-coding RNA, as well as mRNA, a coding RNA transcript, make up ceRNET. These components play a crucial role in post-transcriptional regulation and are involved in the diagnosis and treatment of many pathological disorders. The mechanism of ceRNET and its essential components, as well as their therapeutic implications in different diseases such as cancer, diabetes mellitus, neurological, cardiovascular, hepatic and respiratory disorders were covered in this review.

摘要

不同的疾病可能源于非编码RNA(ncRNA)的失调,而这种调节对于维持细胞内稳态是必要的。ncRNA受转录、转录后、翻译和翻译后过程的调控。基因表达的转录后调控由微小RNA(miRNA)执行,miRNA是一类小的ncRNA分子,它们可以通过存在于miRNA种子序列和靶转录本上的一段简短核苷酸序列(称为miRNA反应元件,MRE)来识别其靶位点。miRNA与靶标之间的这种结合可通过抑制翻译或降解靶信使RNA(mRNA)来调节基因表达。共享MRE的转录本可能会参与对中央miRNA池的竞争,这可能会对彼此的调节产生间接影响。这种竞争网络称为竞争性内源RNA网络(ceRNET)。许多ncRNA,包括环状RNA、假基因和长链非编码RNA,以及编码RNA转录本mRNA,构成了ceRNET。这些成分在转录后调控中起关键作用,并参与许多病理疾病的诊断和治疗。本文综述了ceRNET的机制及其重要组成部分,以及它们在癌症、糖尿病、神经、心血管、肝脏和呼吸系统疾病等不同疾病中的治疗意义。

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