Prognostic value of lncRNA DARS-AS1 in colorectal cancer and its regulatory effect on tumor progression
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Qiaoyu Chen1, Qijin Xu2, Li Zhang3
1Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
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.
