Background <p>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.</p> Methods <p>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.</p> Results <p>Serum DARS-AS1 was elevated in CRC patients (<i>P</i> &lt; 0.001), and distinguished them with an area under the curve (AUC) of 0.856. High DARS-AS1 was associated with adverse clinicopathological features (<i>P</i> &lt; 0.05), shorter low disease-free survival (<i>P</i> = 0.008), and worse prognosis [hazard ratio (HR) = 2.400, <i>P</i> = 0.011]. DARS-AS1 was up-regulated in CRC cells (<i>P</i> &lt; 0.001), and silencing it suppressed malignant behavior (<i>P</i> &lt; 0.05). Serum miR-188-5p was down-regulated in CRC patients (<i>P</i> &lt; 0.001), and had a target relationship with DARS-AS1 (<i>r</i> = − 0.733, <i>P</i> &lt; 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 (<i>P</i> &lt; 0.05).</p> Conclusions <p>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.</p>

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

  • Qiaoyu Chen,
  • Qijin Xu,
  • Li Zhang

摘要

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.