Dysregulation of the miR-424-3p/5p–lncRNA MEG3 axis in colorectal cancer: a case-control expression study

Abstract

Colorectal Cancer (CRC) pathogenesis is multifactorial include interactions between long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). This study aimed to evaluate the expression levels of molecular parameters include lncRNA MEG3 and miR-424 (3p/5p) in both blood and tissue of CRC patients. A case-control study was conducted to estimate the hematological parameters including Hemoglobin (Hb), Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets (PLT). Expression levels of MEG3 and miR-424-3p/5p were quantified using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in blood and tissue samples from both CRC patients and healthy controls. Fold expression was performed using 2^-ΔΔCt method, Receiver Operating Characteristic (ROC) curve analysis for diagnostic accuracy, and Spearman’s rank correlation to explore the associations between molecular parameters, age, and hematological parameters. In CRC patients, MEG3 was significantly downregulated in blood and tissue relative to controls (p < 0.001). A comparison found significant upregulation of miR-424-3p and miR-424-5p (p < 0.0001), with miR-424-5p showing the largest fold change in tissue (Median = 3.345). Overall, ROC analysis confirmed that miR-424-3p in blood represents the effective diagnostic parameter (Area under curve - AUC = 0.934, Sensitivity 92%, Specificity 96%). MEG3-B negatively correlated significantly with miR-424-3p-B (rho = −0.520, p = 0.0001). In addition, there was a significant positive correlation between MEG3 levels and Hb and RBC counts and between miR-424-5p and platelet counts (p = 0.0078). Together, these findings indicate that dysregulation of the MEG3/miR-424 axis is associated with CRC and may contribute to its underlying molecular mechanisms. Blood MEG3 expression and tumor miR-424-3p/miR-424-5p expression emerged as independent variables associated with CRC in the multivariable analysis. Furthermore, circulating miR-424-3p demonstrated promising diagnostic performance as a potential non-invasive biomarker for CRC detection. However, these findings should be interpreted cautiously and require validation in larger independent cohorts.