RUNX1 promotes colorectal cancer progression by activating SERPINE1 transcription

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.