Role of miR-21 in the growth and metastasis of human salivary adenoid cystic carcinoma

Mol Med Rep. 2018 Mar;17(3):4237-4244. doi: 10.3892/mmr.2018.8381. Epub 2018 Jan 5.

Abstract

Aberrant microRNA (miRNA/miR) expression has been reported in various cancer types. miR‑21, which is considered to be a proto-oncogene and is frequently overexpressed in certain cancer types, has been implicated in tumorigenesis. The aim of the present study was to investigate the effect of miR‑21 degradation on tumor progression and its potential mechanisms in human salivary adenoid cystic carcinoma (SACC) development. Results of reverse transcription‑quantitative polymerase chain reaction analysis indicated that SACC cells with high metastatic potential (SACC‑LM cells) exhibited a significantly higher expression of miR‑21 compared with SACC cells with a lower metastatic potential (SACC‑83 cells). In addition, following transfection of SACC‑LM cells with miR‑21 inhibitor, cell viability was reduced, which may be a result of reduced cell proliferation and metastasis, and the induction of apoptosis, as determined by Cell Counting Kit‑8, wound healing, Matrigel invasion and flow cytometry assays. Furthermore, bioinformatics analysis indicated that programmed cell death 4 (PDCD4), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B‑cell lymphoma (Bcl)‑2 are potential target genes of miR‑21. Therefore, western blotting was performed to investigate the expression of these proteins, and the results demonstrated that miR‑21 expression level was negatively associated with PDCD4 and PTEN protein expression, and positively associated with Bcl‑2 protein expression, in SACC‑LM cells, indicating that miR‑21 may promote SACC progression via PDCD4, PTEN and Bcl‑2. In conclusion, the present study indicates that miR‑21 may be a novel target for SACC therapy and provide a novel basis for the clinical treatment of SACC.

Keywords: microRNA-21; salivary adenoid cystic carcinoma; proliferation; migration; invasion.

MeSH terms

  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Line, Tumor
  • Cell Migration Assays
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA Stability
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology
  • Signal Transduction

Substances

  • Antagomirs
  • Apoptosis Regulatory Proteins
  • BCL2 protein, human
  • MAS1 protein, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2
  • RNA-Binding Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human