PAG1 stimulates proliferation and metastasis of nasopharyngeal carcinoma through downregulating PTEN

Eur Rev Med Pharmacol Sci. 2020 Nov;24(21):11096-11104. doi: 10.26355/eurrev_202011_23596.

Abstract

Objective: We aim to uncover the expression pattern and biological functions of PAG1 in the progression of nasopharyngeal carcinoma (NPC).

Patients and methods: PAG1 levels in 28 paired NPC tissues and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, the potential influences of PAG1 on proliferative, migratory and invasive abilities of SUNE2 and CNE2 cells were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Next, the interaction between PAG1 and its direct target gene of phosphate and tension homology deleted on chromosome ten (PTEN) was verified by Dual-Luciferase reporter gene assay. At last, rescue experiments were conducted to uncover the role of PAG1/PTEN axis in the malignant progression of NPC.

Results: PAG1 was highly expressed in NPC tissues and cell lines. Knockdown of PAG1 blocked NPC cells to proliferate, migrate, and invade. Dual-Luciferase reporter gene assay indicated the binding relationship between PAG1 and PTEN. In addition, both mRNA and protein levels of PTEN were negatively regulated by PAG1 in NPC cells. Notably, PTEN was responsible for PAG1-regulated malignant progression of NPC.

Conclusions: PAG1 is upregulated in NPC tissues and cells and stimulates the proliferative and metastatic abilities in NPC by targeting PTEN, thus aggravating the malignant progression of NPC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nasopharyngeal Carcinoma / metabolism*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Membrane Proteins
  • PAG1 protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human