Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma

J Oral Pathol Med. 2019 Jan;48(1):52-59. doi: 10.1111/jop.12787. Epub 2018 Oct 23.

Abstract

Background: Noxa, which is subset of the Bcl-2 family of proteins, was previously reported to have considerable therapeutic potential in diverse cancers. However, its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not been well studied. This study aimed to elucidate the expression and role of Noxa in salivary gland ACC.

Materials and methods: The expression levels of NOXA and its association with overall survival in salivary gland ACC were analyzed by quantitative real-time PCR. We next examined the effects of Noxa overexpression or inhibition on colony formation, proliferation, apoptosis, and autophagy of salivary gland ACC cells. Furthermore, promoter analysis was performed to identify the potential transcriptional activator of NOXA.

Results: NOXA was markedly down-regulated and significantly correlated with a more aggressive phenotype and poor overall survival of salivary gland ACC. Ectopic expression of Noxa suppressed the viability and growth of ACC cells, which involved the induction of apoptosis and autophagy. Moreover, the transcriptional activity of NOXA gene could be enhanced by p53.

Conclusion: The findings of this study indicate that Noxa, activated transcriptionally by p53, suppress the progression of ACC, whereby it regulates proliferation, apoptosis, and autophagy.

Keywords: Noxa; adenoid cystic carcinoma; apoptosis; autophagy; cell proliferation.

MeSH terms

  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / pathology*
  • Cell Proliferation / genetics*
  • Disease Progression
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / pathology*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology

Substances

  • PMAIP1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53