EMT in salivary gland tumors: the expression of microRNAs miR-155 and miR-200c is associated with clinical-pathological parameters

Mol Biol Rep. 2022 Mar;49(3):2157-2167. doi: 10.1007/s11033-021-07033-1. Epub 2022 Jan 4.

Abstract

Background: Epithelial to mesenchymal transition promotes cell adhesion loss, enabling invasion and metastasis. MicroRNAs are a class of small non-codifying RNAs that regulate gene expression.

Objectives: The aim of this study was to evaluate the expression of microRNAs that could regulate the expression of EMT factors in salivary gland tumors (SGTs).

Methods and results: The expression of microRNAs miR-9, miR-34a, miR-101, miR-138, miR-155, and miR-200c-described in the literature to target EMT factors-was evaluated by Real-time RT-PCR (qPCR) in pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) samples. Bioinformatics tools were applied to identify miR targets and immunohistochemistry was used to examine the expression of the proteins E-cadherin, Twist, ZEB-1, β-Catenin, and c-Kit. Comparing miR expression among SGT types, we observed increased expression of miR-9, and miR-138 in PAs, and increased miR-155 expression in MECs. Low-grade MECs exhibited increased miR-155 expression (p = 0.032). MECs that generated lymph node metastases had increased miR-200c levels (p = 0.018). MECs tended to have decreased expression of EMT-related proteins when compared to the other SGT types (c-Kit p < 0.001, Twist p = 0.014, and ZEB p = 0.012). Notably, increased c-Kit expression was associated with the presence of perineural infiltration in ACC (p = 0.050).

Conclusions: This study provides evidence of alterations in the expression of EMT-factors regulating miRs, especially of miR-9, miR-138, miR-155, and miR-200c. No significant relationships were found between the expression of these miRs and proteins associated with EMT in SGTs.

Keywords: Epithelial-mesenchymal transition; Immunohistochemistry; Salivary gland tumors; miRNAs; qPCR.

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Salivary Gland Neoplasms* / genetics

Substances

  • Cadherins
  • MIRN138 microRNA, human
  • MIRN155 microRNA, human
  • MIRN200 microRNA, human
  • MIRN92 microRNA, human
  • MicroRNAs