piR-37524 Overexpression in Colorectal Cancer:A Potential Diagnostic Bio-Marker and Therapeutic TargetOA

Objectives: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.Methods: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.Results: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.Conclusions: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.