HSD17B2 serves as a novel tumor-suppressive regulator in colorectal cancer progression

Colorectal Cancer (CRC) ranks as one of the most prevalent malignancies worldwide, characterized by substantial incidence and mortality rates. Despite its clinical importance, the molecular mechanisms underlying CRC pathogenesis remain incompletely elucidated. In this study, we conducted a comprehensive analysis of transcriptomic datasets obtained from the Gene Expression Omnibus (GEO) database (GSE103512, GSE39923, GSE44076, and GSE68468). By integrating differential expression analysis and weighted gene co-expression network analysis (WGCNA), we identified key molecular signatures associated with CRC. Among them, HSD17B2 emerged as a consistently downregulated gene across multiple analyses, including single-cell RNA Sequencing (scRNA-seq) using a previously published dataset (GSE221575) containing human colorectal tumors and matched adjacent normal tissues, clinical CRC tissue samples, and an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced murine CRC model. Functional characterization using three human CRC cell lines (Caco-2, HT-29, and HCT-116) demonstrated that ectopic expression of HSD17B2 significantly suppressed cellular proliferation and colony formation. These findings suggest that HSD17B2 acts as a novel negative regulator in CRC and provide mechanistic insights into CRC pathogenesis that may inform future therapeutic strategies.

Colorectal cancer; HSD17B2.