表达HPV16/18 E7的重组腺病毒在C33A细胞中调高HDAC6和DNMT3B基因
Yunting Shao1, Pir Tariq Shah1, Qisheng Su1
1Faculty of Medicine, School of Basic Medical Sciences, Dalian University of Technology, Dalian, China.
Frontiers in cellular and infection microbiology
|October 16, 2024
概括
高风险的人类乳头瘤病毒 (HPV) E6和E7蛋白质通过上调HDAC6和DNMT3B来驱动子宫癌. 这些基因在癌症途径中至关重要,为HPV相关癌症提供潜在的治疗点.
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:
- 高风险的人类乳头瘤病毒 (HPV) 与宫,门和口腔癌有关.
- HPV E6 和 E7 瘤蛋白是细胞转化和癌症发展的关键驱动因素.
- 需要进一步调查HPV E6/E7对宿主蛋白质的全部影响.
研究的目的:
- 研究HPV16/18 E6和E7瘤原蛋白对宿主细胞蛋白质的全球调控作用.
- 通过HPV E6/E7表达,在宫癌细胞中识别差异表达基因 (DEGs).
- 探索DEG与关键癌症相关信号通路的相关性.
主要方法:
- 构建表达HPV16/18 E6,E7或两者的复合腺病毒.
- 感染C33A宫癌细胞以持续的E6/E7表达.
- RNA测序 (RNA-Seq) 用于转录组分析和DEGs的识别.
- 定量逆转录PCR (qRT-PCR) 和西布洛特用于基因表达验证.
主要成果:
- 过度表达的HPV16/18 E6/E7上调的GP6,CD36,HDAC6,ESPL1和DNMT3B. 这种过度表达.
- HDAC6和DNMT3B与DNA复制,增殖,G2M检查点,p53和PI3K/AKT/mTOR通路有显著的相关性.
- 证实HPV16/18 E7可上调HDAC6和DNMT3B的表达.
结论:
- 再组合腺病毒成功表达了HPV16/18 E6/E7,保留了感染力.
- 在HPV16/18 E7上调HDAC6和DNMT3B,影响细胞周期和癌症途径.
- HDAC6和DNMT3B是HPV相关癌症的潜在治疗点,需要进一步研究E6/E7的瘤机制.
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