转录组和多层变异分析确定STAT3和HIF1A是肺状细胞癌中受调节的细胞死亡途径的中央调节者
Xiaolei Li1, Awais Ali2, Syed Luqman Ali3,4
1Department of Pathology, Linfen Central Hospital, Linfen City, Shanxi Province, 041000, China.
Naunyn-Schmiedeberg's archives of pharmacology
|February 19, 2026
概括
这项研究确定了STAT3和HIF1A作为肺状细胞癌 (LUSC) 中细胞死亡的关键调节者. 这些调节者的有害遗传变异可能导致瘤的进展和对治疗的抗性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 肺状细胞癌 (LUSC) 是一种具有高死亡率和治疗耐药性的侵袭性非小细胞肺癌 (NSCLC) 亚型.
- 调节细胞死亡 (RCD) 途径在LUSC中至关重要,影响瘤命运和治疗反应,但它们的调节者不明.
研究的目的:
- 为了确定转录调节器和基因变异控制RCD路径在LUSC.
- 阐明这些调节剂在LUSC进展和治疗耐药性的作用.
主要方法:
- 多个GEO数据集的综合性转录组分析.
- 功能丰富分析 (GO,KEGG) 和蛋白质与蛋白质相互作用网络分析 (STRING,Cytoscape).
- 预测和验证上游的转录调节剂 (iRegulon,UALCAN,TCGA,HPA).
- 在关键转录因子中对高影响非同义SNP (nsSNP) 进行优先级和结构建模.
主要成果:
- 确定了STAT3和HIF1A作为中央调节器,在LUSC中将亡和亡联系起来,参与低氧反应和TNF/NF-κB信号传递.
- STAT3和HIF1A的高表达与LUSC的整体存活率较差相关.
- 预计STAT3和HIF1A中的有害nsSNP会破坏蛋白质结构和功能,可能影响转录调节.
结论:
- 在LUSC中,STAT3和HIF1A是apoptotic和necroptotic交叉对话的关键调节者.
- 在STAT3和HIF1A中的基因变异代表了LUSC.基于精度的治疗干预的潜在脆弱性.
- 需要进一步的研究来验证这些调节剂及其变体的预后作用和治疗向.
更多相关视频
11:19Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
16.1K
11:50Genome-Wide Mapping of Histone Modifications and Transcription Factor Binding Sites in Neuroendocrine Small Cell Lung Cancer Cell Lines Using CUT&RUN
Published on: April 3, 2026
112
相关概念视频
02:23Abnormal Proliferation
4.0K
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...
4.0K
01:24Regulation of Angiogenesis and Blood Supply
2.9K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
01:20The JAK-STAT Signaling Pathway
10.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
10.2K
01:23Regulation of Expression at Multiple Steps
1.4K
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...
1.4K