N-α-Acetyltransferase 10 inhibits invasion and metastasis of oral squamous cell carcinoma via regulating Pirh2-p53 signalling pathway

J Cell Mol Med. 2022 May;26(10):2921-2934. doi: 10.1111/jcmm.17306. Epub 2022 Apr 2.

Abstract

N-α-Acetyltransferase 10 (NAA10) was reported to be involved in tumour invasion and metastasis in several of tumours. However, the role and mechanism of NAA10-mediated invasion and metastasis in oral squamous cell carcinoma (OSCC) remains undetermined. Herein, our study showed that NAA10 inhibits cell migration and invasion in vitro and attenuates the xenograft tumorigenesis in nude mice. Mechanistically, we demonstrated that there is a physical interaction between NAA10 and RelA/p65 in OSCC cells, thereby preventing RelA/p65-mediated transcriptional activation of Pirh2. Consequently, inhibition of Pirh2 increased p53 level and suppressed the expression of p53 downstream targets, matrix metalloprotein-2 (MMP-2) and MMP-9. Therefore, NAA10 may function as a tumour metastasis suppressor in the progression of OSCC by targeting Pirh2-p53 axis and might be a prognostic marker as well as a therapeutic target for OSCC.

Keywords: NAA10; OSCC; Pirh2-p53; invasion; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Mouth Neoplasms* / pathology
  • N-Terminal Acetyltransferase A* / metabolism
  • N-Terminal Acetyltransferase E* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases

Substances

  • Tumor Suppressor Protein p53
  • N-Terminal Acetyltransferase A
  • NAA10 protein, human
  • N-Terminal Acetyltransferase E
  • RCHY1 protein, human
  • Ubiquitin-Protein Ligases