在威尔姆斯瘤中,PD-L1表达通过microRNA处理,Wnt/β-Catenin信号传输和化疗进行介导
Patricia D B Tiburcio1, Kavita Desai2,3, Austin Warne1
1Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Pediatric blood & cancer
|June 13, 2025
概括
免疫检查点蛋白PD-L1在威尔姆斯瘤子集中被上调,特别是在化疗后. 在CTNNB1和DROSHA中的突变也与更高的PD-L1相关,为儿科癌症治疗提供信息.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 儿科研究 儿科研究
背景情况:
- 与成人癌症相比,免疫检查点抑制在儿童癌症中表现出有限的成功.
- 像PD-L1这样的免疫检查点蛋白的调节在儿科恶性瘤中了解得很少.
研究的目的:
- 为了研究在威尔姆斯瘤中PD-L1表达的调节,这是最常见的儿科癌.
- 确定与儿科癌症PD-L1上调相关的临床和生物因素.
主要方法:
- 使用反相蛋白质阵列的无监督聚类对威尔姆斯瘤样本的分析.
- 使用已公布的测序数据,流细胞计和免疫血栓验证发现.
- 在体外实验中评估PD-L1通过化疗药物调节,Wnt/β-catenin信号传递和基因淘汰 (DROSHA,DICER1).
主要成果:
- 在威尔姆斯瘤的不同子集中,PD-L1被上调.
- 化疗暴露和常见的化疗药物在体外增加PD-L1表达.
- 在CTNNB1和DROSHA中的突变,以及Wnt/β-catenin激活和DROSHA/DICER1敲击,与PD-L1水平相关或增加.
结论:
- 已经确定了在威尔姆斯瘤中调节PD-L1的临床和生物因素.
- 这些发现可以指导小儿免疫瘤学准确治疗策略的开发.
相关概念视频
Canonical Wnt Signaling Pathway
8.7K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
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
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
Non-Canonical Wnt Signaling Pathways
7.3K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
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
lncRNA - Long Non-coding RNAs
8.5K
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...
8.5K


