在肝细胞癌中,CPSF3促进了mRNA前分离,并防止了circRNA循环
Ying Huang1, Haofei Ji1, Jiani Dong1
1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Cancers
|August 26, 2023
概括
高水平的CPSF3通过减少圆形RNAs (circRNAs) 和增加线性mRNAs来促进肝细胞癌 (HCC). 使用JTE-607抑制CPSF3抑制了HCC细胞的增殖,提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 循环RNAs (circRNAs) 在瘤发生和转移中发挥作用,但在肝细胞癌 (HCC) 中被下调.
- 循环RNA的逆向拼接与3'-end拼接有关,这表明3'-end处理因子可能发挥作用.
研究的目的:
- 调查CPSF3,一个核心3'-end裂变因子在HCC病变发生和circRNA调节中的作用.
- 探索CPSF3作为HCC的预后标志物和治疗点.
主要方法:
- 对预后相关性临床数据的分析.
- 细胞学实验和光记者试验用于研究CPSF3的功能和机制.
- RNA测序和PCR用于识别CPSF3调节的环RNAs.
- 在体外和体内对CPSF3抑制剂JTE-607的研究.
主要成果:
- CPSF3在HCC中高度表达,与预后不佳相关,并促进细胞增殖和迁移.
- CPSF3增强了RNA裂变,导致circRNA水平降低和线性mRNA增加.
- 通过JTE-607抑制CPSF3,抑制了HCC细胞的增殖,在体外和体内.
结论:
- 在HCC中增加的CPSF3驱动了从circRNA转向线性mRNA生产的转变,促进了不受控制的细胞增殖.
- CPSF3是一种潜在的预后生物标志物和HCC的治疗标.
- 通过抑制CPSF3.3,JTE-607证明了对HCC的治疗潜力.
相关概念视频
RNA Splicing
56.5K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.5K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.0K
Alternative RNA Splicing
21.3K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.3K
Nonsense-mediated mRNA Decay
10.7K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.7K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Pre-mRNA Processing: RNA Splicing
5.3K
5.3K


