Yang Yueyan, Deng Shihua, Yin Qing, Zhang Ting, Liu Teng, Wu Dongming, Xu Ying
School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610500, PR China; The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, PR China.
School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610500, PR China; The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, PR China.
Biochem Biophys Res Commun. 2025 May 26;760:151732. doi: 10.1016/j.bbrc.2025.151732. Epub 2025 Mar 28.
Colorectal cancer (CRC) is among the most prevalent malignancies affecting the digestive system globally, considerably endangering public health. Runt-related transcription factor 1 (RUNX1) is a key regulator that influences the progression of cancer. In this study, we investigated the involvement of RUNX1 in CRC progression and its underlying mechanisms.
The expression levels and prognostic significance of RUNX1 in CRC were analyzed based on data from the TNMplot, Gene Expression Profiling Interactive Analysis, and Gene Expression Omnibus databases as well as tissue microarrays. RUNX1 was knocked down or overexpressed in HT29 and HCT116 cells. The proliferation, migration, and invasion of CRC cells were evaluated. The target gene of RUNX1 was identified using PCR array analysis and validated via chromatin immunoprecipitation and luciferase reporter assays. The effects of RUNX1 on CRC cells were verified in vivo.
RUNX1 expression in CRC tissues was significantly higher than that in adjacent non-tumorous tissues and was associated with an unfavorable prognosis. Silencing RUNX1 significantly suppressed the proliferation, migratory capability, and invasive potential of CRC cells; overexpressing RUNX1 had the opposite effect. SERPINE1 was identified as a direct transcriptional target of RUNX1. In vivo experiments further validated that RUNX1-promoted CRC tumor growth. Mechanistically, RUNX1 promotes CRC progression by promoting the transcription of SERPINE1.
Our findings revealed that RUNX1 promotes CRC progression by activating SERPINE1 transcription, suggesting that RUNX1 is a potential prognostic biomarker and therapeutic target in CRC.
结直肠癌（CRC）是全球影响消化系统的最常见恶性肿瘤之一，严重危害公众健康。 runt相关转录因子1（RUNX1）是影响癌症进展的关键调节因子。在本研究中，我们调查了RUNX1在CRC进展中的作用及其潜在机制。
基于TNMplot、基因表达谱交互式分析和基因表达综合数据库以及组织芯片的数据，分析RUNX1在CRC中的表达水平和预后意义。在HT29和HCT116细胞中敲低或过表达RUNX1。评估CRC细胞的增殖、迁移和侵袭能力。使用PCR阵列分析鉴定RUNX1的靶基因，并通过染色质免疫沉淀和荧光素酶报告基因检测进行验证。在体内验证RUNX1对CRC细胞的影响。
CRC组织中RUNX1的表达明显高于相邻非肿瘤组织，且与不良预后相关。沉默RUNX1可显著抑制CRC细胞的增殖、迁移能力和侵袭潜能；过表达RUNX1则产生相反的效果。SERPINE1被鉴定为RUNX1的直接转录靶标。体内实验进一步证实RUNX1促进CRC肿瘤生长。机制上，RUNX1通过促进SERPINE1的转录促进CRC进展。
我们的研究结果表明，RUNX1通过激活SERPINE1转录促进CRC进展，提示RUNX1是CRC潜在的预后生物标志物和治疗靶点。
