MiR-26a and miR-191 are upregulated while PLAG1 and HIF2 are downregulated in pleomorphic adenomas of the salivary glands compared to Warthin tumors

J Oral Pathol Med. 2024 Aug;53(7):451-457. doi: 10.1111/jop.13565. Epub 2024 Jun 9.

Abstract

Background: Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR-26a, miR-26b, and miR-191), and three pro-oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers.

Methods: This cross-sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction.

Results: All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR-26a And miR-191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH.

Conclusion: The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR-26a, miR-191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers.

Keywords: HIF2; MTDH; PLAG1; micro‐RNA; salivary gland tumors.

Publication types

  • Comparative Study

MeSH terms

  • Adenolymphoma* / genetics
  • Adenolymphoma* / pathology
  • Adenoma, Pleomorphic* / genetics
  • Adenoma, Pleomorphic* / metabolism
  • Adenoma, Pleomorphic* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors* / genetics
  • Biomarkers, Tumor
  • Cross-Sectional Studies
  • DNA-Binding Proteins*
  • Diagnosis, Differential
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins*
  • MicroRNAs*
  • Middle Aged
  • RNA-Binding Proteins
  • Salivary Gland Neoplasms* / genetics
  • Salivary Gland Neoplasms* / metabolism
  • Salivary Gland Neoplasms* / pathology
  • Up-Regulation*

Substances

  • MicroRNAs
  • PLAG1 protein, human
  • endothelial PAS domain-containing protein 1
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Membrane Proteins
  • Biomarkers, Tumor
  • RNA-Binding Proteins
  • MTDH protein, human
  • MIRN126 microRNA, human