长非编码RNA HOX转录反意义跨基因RNA枯竭通过microRNA-148a-3p/sphingosine 1-phosphate受体1轴对酒精性肝炎进行保护
Dan Chen1, Ping Lu2, Tianfeng Sun3
1Department of Integrated TCM & Western Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, 215101, People's Republic of China.
Cell and tissue research
|October 18, 2023
概括
长非编码RNAHOTAIR通过促进肝星细胞增殖,使酒精性肝炎 (AH) 肝损伤恶化. 针对HOTAIR/miR-148a-3p/S1PR1通路可能提供新的AH疗法.
科学领域:
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
- 在RNA生物学,RNA生物学.
背景情况:
- 长非编码RNAHOTAIR与肝损伤有关.
- 在酒精性肝炎 (AH) 引起的肝损伤中HOTAIR的作用尚不清楚.
- 肝星细胞激活是肝纤维化的一个关键因素.
研究的目的:
- 调查lncRNA HOTAIR在肝星细胞活力和AH的亡中的作用.
- 阐明HOTAIR在AH中影响肝损伤的分子机制.
- 探索AH的潜在治疗点.
主要方法:
- 在老鼠中AH的动物模型.
- 功能丧失测定 (HOTAIR静音) 的方法.
- 生物信息学分析,双露西法酶记者测定,RNA免疫沉 (RIP) 和光在位杂交 (FISH) 测定.
- 进行救援实验.
主要成果:
- HOTAIR和S1PR1在AH老鼠肝脏中受到上调,而miR-148a-3p在AH老鼠肝脏中受到下调.
- 沉默HOTAIR缓解了AH大鼠的肝损伤,HSC激活,炎症和纤维化.
- 霍泰尔与miR-148a-3p结合,而miR-148a-3p针对S1PR1,形成霍泰尔/米R-148a-3p/S1PR1轴.
- 抑制miR-148a-3p或S1PR1的过度表达逆转了HOTAIR沉默的保护作用.
结论:
- 霍泰尔通过miR-148a-3p/S1PR1通路促进肝星细胞增殖和AH中的肝损伤.
- HOTAIR/miR-148a-3p/S1PR1轴代表了酒精性肝炎的潜在治疗目标.
- 进一步的研究可能会导致AH的新型治疗策略.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
8.6K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.6K
01:22MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
02:15Experimental RNAi
6.1K
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...
6.1K
01:58Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
02:30siRNA - 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
01:23RNA 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