异形性肺纤维化分子基质由竞争的内源性RNA调节网络揭示
Muhammed Fatih Kircali1,2, Beste Turanli2
1School of Medicine, Marmara University, Istanbul, Türkiye.
Omics : a journal of integrative biology
|August 4, 2023
概括
这项研究揭示了异常性肺纤维化 (IPF) 中的关键分子参与者,通过构建一个信使RNA (mRNA) -微RNA (miRNA) -循环RNA (circRNA) 调节网络. 这些发现为IPF机制和潜在的治疗点提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 系统生物学 系统生物学
- 肺部医学 肺部医学
背景情况:
- 异形性肺纤维化 (IPF) 是一种进展性肺病,治疗选择有限.
- 微RNAs (miRNAs) 和循环RNAs (circRNAs) 在IPF病变发生中的作用尚不清楚.
- 了解基因调节网络对于识别新型治疗策略至关重要.
研究的目的:
- 在IPF中构建一个信使RNA (mRNA) -miRNA-circRNA竞争的内源RNA (ceRNA) 调控网络.
- 通过系统生物学方法,识别IPF的新型分子特征和潜在的治疗点.
主要方法:
- 利用六个基因表达数据集来识别差异表达基因 (DEGs) 和miRNAs (DEmiRNAs).
- 构建了蛋白质-蛋白质相互作用,mRNA-miRNA和miRNA-circRNA网络.
- 通过Drug Gene Budger平台分析了网络模块,并确定了枢纽基因和潜在的治疗化合物.
主要成果:
- 确定了724种常见的DEG和278种DEmiRNA.
- 在蛋白质-蛋白质相互作用网络中发现了包括TMPRSS4,ESR2,TP73,CLEC4E和TP63在内的关键枢纽基因.
- 揭示了两个重要的mRNA-miRNA模块,包括ADRA1A,ADRA1B,hsa-miR-484,CDH2,TMPRSS4和hsa-miR-543,并提出了潜在的circRNA调节器.
结论:
- 开发的ceRNA网络加深了对IPF分子机制的理解.
- 已识别的分子特征和枢纽基因可以作为IPF诊断的新生物标志物.
- 这些发现为开发IPF创新的诊断和治疗方法提供了基础.
相关概念视频
RNA Interference
26.1K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.1K
Experimental RNAi
6.2K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.2K
siRNA - Small Interfering RNAs
16.8K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.8K
Cystic Fibrosis: Pathogenesis
281
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
281
piRNA - Piwi-interacting RNAs
6.9K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.9K
Translational Regulation
45
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
45


