Jia Yongqin, Yang Neng, Tang Shuai, Deng Li, Wang Yanzhou, Cai Xiongwei
Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, China.
Sci Rep. 2025 Jan 2;15(1):497. doi: 10.1038/s41598-024-84254-x.
As cervical cancer (CC) caused more than 300,000 deaths in the world, it is urgent to identify therapeutic targets to improve survival. Though RUNX1 is overexpressed in CC, its specific role and underlying molecular mechanisms remain incompletely understood. Here we presented that RUNX1 was upregulated in CC and associated with poor prognosis. Functional studies demonstrated that RUNX1 acts as an oncogene in CC, with overexpression accelerating cell cycle progression and promoting cell proliferation. Mechanistically, RUNX1 regulates the MAPK pathway by modulating TGFB2 expression, while TGFB2 inhibition impaired MAPK pathway activation and the proliferation driven by RUNX1 overexpression. Comprehensive analyses also suggested that RUNX1 may modulate the immune microenvironment in CC through TGFB2. These findings indicate that RUNX1 promotes CC progression by activating the MAPK pathway through upregulation of TGFB2. Our study provides new insights into the role of RUNX1 in CC proliferation and suggests RUNX1 as a potential therapeutic target in CC.
由于宫颈癌（CC）在全球导致超过30万人死亡，因此确定治疗靶点以提高生存率迫在眉睫。尽管RUNX1在CC中过表达，但其具体作用和潜在分子机制仍未完全明确。在此我们指出，RUNX1在CC中上调并与不良预后相关。功能研究表明，RUNX1在CC中作为癌基因发挥作用，其过表达加速细胞周期进程并促进细胞增殖。机制上，RUNX1通过调节TGFB2表达来调控MAPK通路，而抑制TGFB2会损害MAPK通路激活以及RUNX1过表达驱动的增殖。综合分析还表明，RUNX1可能通过TGFB2调节CC中的免疫微环境。这些发现表明，RUNX1通过上调TGFB2激活MAPK通路来促进CC进展。我们的研究为RUNX1在CC增殖中的作用提供了新见解，并提示RUNX1作为CC的潜在治疗靶点。
