Hypermethylation of miR-129-2-3p inhibits esophageal cancer proliferation and migration by down-regulating PPP6C expression.

Abstract

Objective: MicroRNAs (miRNAs) play crucial roles in gene regulation, and their dysregulation is associated with various diseases, including cancer. Abnormal DNA methylation can alter gene expression and influence carcinogenesis. DNA methylation-based biomarkers are emerging as promising tools for early cancer diagnosis. This study aimed to investigate the role of miR-129-2-3p in esophageal cancer (EC) and explore its potential as a diagnostic biomarker.

Methods: To achieve these objectives, we employed multi-sample MethylTarget technology to assess the methylation status of miR-129-2-3p in EC tissues. The diagnostic value of miR-129-2-3p was evaluated using logistic regression and receiver operating characteristic (ROC) curve analysis. Functional assays were conducted to examine the effects of miR-129-2-3p overexpression on EC cell proliferation and migration. Luciferase reporter assays were performed to confirm Protein Phosphatase 6 Catalytic Subunit (PPP6C) as a direct target of miR-129-2-3p. Finally, the impact of PPP6C overexpression on the inhibitory effects induced by miR-129-2-3p was assessed.

Results: We found that miR-129-2-3p is hypermethylated in EC tissues. Diagnostic analysis revealed that miR-129-2-3p had a sensitivity of 0.884, a specificity of 0.659, and an area under the curve (AUC) of 0.799. Overexpression of miR-129-2-3p significantly suppressed EC cell proliferation and migration. Furthermore, PPP6C was identified as a direct target of miR-129-2-3p, and its expression was suppressed. The elevation of PPP6C counteracted the inhibitory effects of miR-129-2-3p on EC cell proliferation and migration.

Conclusion: Hypermethylated miR-129-2-3p inhibits EC cell proliferation and migration by downregulating PPP6C expression, suggesting that miR-129-2-3p may serve as a potential diagnostic biomarker for EC.