Piwi-associated RNAs are small non-coding RNAs implicated in cancer, yet few have been characterized in colorectal cancer (CRC). This study aimed to identify a CRC-related piRNA and investigate its clinical relevance, biological function, and biomarker potential.

Candidates were identified by reanalysis of small-RNA sequencing. piR-37524 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) in colorectal cancer tissues, matched adjacent non-tumor tissues, colorectal adenomas, liver metastases, and serum samples from patients and healthy controls. Clinicopathological correlations and diagnostic performance were evaluated. Functional assays included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation, colony formation, and wound-healing migration in HCT116 and HT29 cells after piR-37524 inhibition. RNA sequencing and Western blotting examined epithelial–mesenchymal transition (EMT) markers and nuclear factor-kappa B (NF-κB) components.

piR-37524 was significantly overexpressed in CRC compared with adjacent non-tumor tissues and was associated with larger tumor size, poorer differentiation, and distant metastasis. Elevated expression was also observed in colorectal adenomas and liver metastases. Serum piR-37524 levels were increased in patients with adenomas and CRC compared with healthy controls, indicating diagnostic potential. Functional assays demonstrated that piR-37524 inhibition suppressed CRC cell proliferation and migration, accompanied by changes consistent with epithelial–mesenchymal transition regulation. Mechanistic analyses implicated tumor necrosis factor alpha-induced protein 3 (TNFAIP3)-associated NF-κB signaling.

piR-37524 is an oncogenic piRNA in CRC that promotes progression via the TNFAIP3/NF-κB/EMT axis, serving as a potential pan-stage diagnostic biomarker and therapeutic target.