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通过E7介导的miR-203抑制促进了LASP1依赖的增殖在HPV阳性宫癌
Molly R Patterson1,2,3, Aniek S Meijers1,2, Emma L Ryder1,2
1School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Oncogene
|May 24, 2024
概括
人类乳头瘤病毒 (HPV) 感染对宫癌中的LASP1蛋白进行上调,促进癌细胞生长. 向LASP1为HPV相关的恶性瘤提供了潜在的新疗法.
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:
- 人类乳头瘤病毒 (HPV) 与全球约5%的癌症有关,特别是宫癌,生殖器癌和口腔癌.
- HPV 瘤基因 E6 和 E7 破坏宿主细胞通路,驱动增殖和生存,这可能导致恶性转变.
- 有效的HPV疫苗存在,但针对HPV驱动的癌症的特定抗病毒疗法和治疗仍然有限,这凸显了对新型治疗点的需求.
研究的目的:
- 为了研究actin结合蛋白LASP1在HPV相关的宫癌中的作用.
- 阐明HPV影响LASP1表达的机制.
- 评估LASP1作为HPV阳性宫癌的潜在治疗标.
主要方法:
- 对LASP1表达与患者生存数据的相关性分析.
- 在体外研究涉及LASP1在HPV阳性和HPV阴性宫癌细胞的枯竭.
- 研究LASP1 SH3域在瘤性中的作用.
- 关于HPV E7调节miR-203及其对LASP1mRNA水平的影响的机制研究.
- 在小鼠模型中进行体内瘤性测定.
主要成果:
- 在宫癌中,LASP1的调节升高,并与较差的存活率有关.
- 在HPV阳性细胞中,LASP1减弱抑制了瘤原体表型,但在HPV阴性细胞中却没有.
- 拉斯普1SH3域对其致癌功能至关重要.
- 由于HPV E7抑制了miR-203,导致LASP1表达的增加.
- 在体内,LASP1表达对瘤生长至关重要.
结论:
- 感染HPV诱导LASP1上调,以促进宫癌细胞的增殖和存活.
- 拉斯普1代表HPV阳性宫癌的潜在治疗标.
- 了解HPV与宿主之间的相互作用,如miR-203/LASP1轴,是开发新癌症治疗方法的关键.
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