在宫癌发生过程中,STAT3和AP1之间的物理相互作用:对HPV转录控制的影响
Kulbhushan Thakur1, Divya Janjua1, Nikita Aggarwal1
1Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India.
Biochimica et biophysica acta. Molecular basis of disease
|August 2, 2023
概括
在宫癌中,信号转换器和转录激活器3 (STAT3) 通过c-FOS和c-JUN间接与HPVDNA相互作用. 这种相互作用会影响病毒蛋白的表达,并影响患者的预后.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 信号转换器和转录3激活器 (STAT3) 的构成性激活与宫癌 (CaCx) 的进展有关.
- STAT3影响人类乳头瘤病毒 (HPV) 转录的确切机制尚不清楚.
研究的目的:
- 调查STAT3和HPV16/18长控制区域 (LCR) 之间的直接和间接相互作用.
- 阐明STAT3在调节病毒蛋白表达中的作用及其对CaCx预后的影响.
主要方法:
- 在HPVLCR上的STAT3结合基因的分析.
- 染色体免疫沉 (ChIP-PCR) 用于验证STAT3结合.
- 同免疫沉和免疫细胞化学评估蛋白质-蛋白质相互作用.
- 接近结合试验以确认STAT3-AP1复合体的形成.
- 在CaCx瘤组织中分析STAT3和c-JUN表达.
主要成果:
- STAT3不会直接与HPV16的LCR结合.
- STAT3与c-FOS和c-JUN进行物理相互作用,与AP1.1形成一个复合体.
- IL-6治疗增强了STAT3/c-FOS/c-JUN的同位化,而静态治疗则减少了它.
- 改变STAT3表达影响c-FOS/c-JUN定位和病毒蛋白 (E6/E7) 表达.
- 高c-JUN表达与HPV16/18 CaCx的预后不佳相关;高STAT3与HPV18 CaCx的预后不佳相关.
结论:
- 通过c-FOS和c-JUN,STAT3间接与HPV的LCR相互作用.
- 这种间接的相互作用增强了病毒coproteins的转录,有助于CaCx的发展.
- STAT3和c-JUN表达水平作为宫癌的潜在预后生物标志物.
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