Prognostic value of lncRNA DARS-AS1 in colorectal cancer and its regulatory effect on tumor progression.

BACKGROUND

Colorectal cancer (CRC) has high incidence and mortality with limited diagnostic and prognostic methods. This study explored the diagnostic and prognostic significance of the DARS-AS1 in CRC, and its regulatory mechanism via miR-188-5p.

METHODS

The clinical significance of serum DARS-AS1 was analyzed using receiver operator characteristic (ROC) curves, Cox regression, the Kaplan-Meier method, and chi-square tests. DARS-AS1 silencing effects on CRC cell behavior were analyzed via CCK-8/Transwell assays. This study identified and validated miR-188-5p target genes using online databases and dual-luciferase reporter assays.

RESULTS

Serum DARS-AS1 was elevated in CRC patients (P < 0.001), and distinguished them with an area under the curve (AUC) of 0.856. High DARS-AS1 was associated with adverse clinicopathological features (P < 0.05), shorter low disease-free survival (P = 0.008), and worse prognosis [hazard ratio (HR) = 2.400, P = 0.011]. DARS-AS1 was up-regulated in CRC cells (P < 0.001), and silencing it suppressed malignant behavior (P < 0.05). Serum miR-188-5p was down-regulated in CRC patients (P < 0.001), and had a target relationship with DARS-AS1 (r = - 0.733, P < 0.001). miR-188-5p target genes-including PTEN, ESR1, and FBXW7-were enriched in CRC-related pathways; FBXW7 was experimentally validated as a direct target (P < 0.05).

CONCLUSIONS

This study identifies serum DARS-AS1 as a non-invasive diagnostic and prognostic biomarker for CRC with superior performance to conventional markers, and elucidates the DARS-AS1/miR-188-5p/FBXW7 axis as a novel mechanistic framework for CRC progression, providing both a clinical tool for risk stratification and targets for molecular therapy.