在骨髓瘤中,ac4C乙化调节mRNA稳定性和翻译效率
Wenjie Zhang1, Jia Gao1, Lei Fan1
1Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, PR China.
Heliyon
|July 24, 2023
概括
通过使用雷莫德林抑制细胞增殖和转移,在骨髓瘤细胞中抑制N4-乙基丁 (ac4C) 乙化. 这种治疗还促进了细胞亡和细胞循环停止,突出显示了ac4C在基因表达中的作用.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 通过增加mRNA稳定性,N4-乙基丁 (ac4C) 乙化增强了基因表达.
- 骨髓瘤是一种重要的骨癌,需要新的治疗点.
- 在骨髓瘤进展中ac4C乙化的作用仍然在很大程度上未被探索.
研究的目的:
- 为了研究ac4C乙化在骨髓瘤中的功能作用.
- 为了确定抑制N-乙转移酶10 (NAT10) 对骨髓瘤细胞行为的影响.
- 在骨髓瘤中通过ac4C乙化调节的目标基因的识别.
主要方法:
- 骨髓瘤细胞系 (U2OS,MG63) 用NAT10抑制剂Remodelin进行治疗.
- 用CCK8试验评估细胞增殖.
- 细胞周期,细胞亡和入侵分别通过流动细胞计和Transwell检测进行了分析.
- 使用乙化RNA免疫沉和测序 (acRIP-seq) 确定了ac4C乙化点.
- 基因和蛋白质表达通过RT-PCR和西方布洛特验证.
主要成果:
- 雷莫德林治疗抑制了NAT10表达和骨肉瘤细胞增殖.
- 观察到G1阶段细胞和亡的显著增加,S阶段细胞的减少.
- 在Remodelin治疗后,细胞侵入性显著降低.
- 鉴定出Farnesyl转移酶子单元β (FNTB) 基因是ac4C乙化的直接标.
结论:
- 抑制ac4C乙化有效抑制骨髓瘤细胞的增殖和转移.
- 向ac4C乙化促进了细胞亡,并诱导了骨髓瘤中的细胞循环停止.
- 在骨髓瘤中,ac4C乙化对于维持目标基因mRNA的稳定性和翻译效率至关重要.
相关概念视频
mRNA Stability and Gene Expression
5.6K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.6K
Regulation of Expression at Multiple Steps
944
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
944
RNA Stability
33.7K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.7K
Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K
Translation
15.0K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
15.0K
Covalently Linked Protein Regulators
6.9K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.9K


