研究FOXO3a与microRNA相互作用以调节瘤发生和发展的进展
Liying Sun1,2, Jiaqi Liu1, Dongbo Bao1
1College of Laboratory Medicine, Jilin Medical University, Jilin, China.
Frontiers in oncology
|November 15, 2023
概括
叉盒O3A (FOXO3a) 蛋白通常抑制瘤,但microRNAs可以改变其功能. FOXO3a和microRNA之间的相互作用影响各种癌症,提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因规则 基因规则
背景情况:
- 众所周知,分叉盒家族蛋白质FOXO3a可以抑制瘤细胞的生长.
- 微RNAs (miRNAs) 调节FOXO3a的表达,而FOXO3a也会影响miRNA水平,从而产生复杂的反循环.
- 了解这些FOXO3a-miRNA相互作用对于癌症研究至关重要.
研究的目的:
- 在五种癌症类型中总结了25个miRNA和FOXO3a之间的调节相互作用.
- 阐明FOXO3a在癌症中的双重作用,作为瘤抑制剂和促进剂.
- 确定参与这些相互作用的关键信号通路.
主要方法:
- 文献综述和现有关于FOXO3a和miRNA在癌症中的相互作用研究的综合.
- 对乳腺癌,肝细胞癌和其他瘤类型中的miRNA-FOXO3a调节关系的分析.
- 在这些相互作用中涉及的信号通路 (PI3K/AKT,Snail,VEGF-NRP1,Wnt/β-catenin) 的识别.
主要成果:
- 双miRNA与FOXO3a协同作用,抑制乳腺癌细胞生长.
- 三个单独的miRNA与FOXO3a合作,抑制肝细胞癌的进展.
- 十二个miRNAs对抗FOXO3a以促进单个瘤细胞的发展,而五个miRNAs促进多种瘤类型的进展.
- 特定的miRNAs (miR-485-5p,miR-498) 可以对抗FOXO3a,在某些情况下促进肝细胞癌的生长.
结论:
- FOXO3a表现出瘤抑制作用,但其功能是取决于上下文的,并由miRNAs调节.
- 特定的FOXO3a-miRNA相互作用可以在各种恶性瘤中抑制或促进癌症的发展.
- 这些发现提供了关于癌症起源的见解,并提供了针对FOXO3a-miRNA通路的潜在新疗法策略.
相关概念视频
MicroRNAs
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
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Regulation of Expression Occurs at Multiple Steps
22.7K
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...
22.7K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Regulation of Expression at Multiple Steps
920
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...
920


