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通过E7介导的miR-203抑制促进了LASP1依赖的扩散在HPV阳性宫癌的LASP1依赖的扩散
bioRxiv : the preprint server for biology
|January 31, 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,促进瘤细胞的生长. 向LASP1为HPV相关癌症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,特别是宫癌有关.
- 目前针对HPV相关癌症的治疗方法有限,这凸显了对新型治疗点的需求.
- 了解HPV对宿主细胞通路的操纵对于开发有效干预措施至关重要.
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.
- 为了确定HPV阳性恶性瘤的潜在治疗点.
主要方法:
- 对LASP1表达与患者存活率的相关性分析.
- 在HPV阳性和阴性宫癌细胞与LASP1枯竭的体外增殖测定.
- 研究LASP1 SH3域在扩散中的作用.
- 分析HPV E7对miR-203的调节及其对LASP1mRNA的影响.
- 在体内瘤性研究.
主要成果:
- 在宫癌中,LASP1的调节升高,并与较差的存活率有关.
- 拉斯普1减少抑制了HPV阳性细胞的增殖,但不能抑制HPV阴性细胞的增殖.
- 拉斯普1SH3域对于HPV阳性细胞的增殖至关重要.
- 由于HPV E7抑制了miR-203,导致LASP1表达的增加.
- 在体内,LASP1对于瘤生长至关重要.
结论:
- 在宫癌中,HPV感染会诱导LASP1的表达,从而促进宫癌的扩散和存活.
- 拉斯普1是HPV驱动性瘤发生的关键媒介.
- 拉斯普1代表着对HPV阳性宫癌的有前途的治疗标.
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