Overexpression of tripartite motif containing 26 inhibits non-small cell lung cancer cell growth by suppressing PI3K/AKT signaling

Kaohsiung J Med Sci. 2020 Jun;36(6):417-422. doi: 10.1002/kjm2.12194. Epub 2020 Feb 12.

Abstract

It has been reported that tripartite motif containing 26 (TRIM26) is involved in the tumorigenesis of some cancers, but its function in non-small cell lung cancer (NSCLC) is still unclear. In this study, we found that TRIM26 was markedly down-regulated in both of NSCLC tumor tissues and cell lines. Additionally, high expression of TRIM26 in NSCLC patients predicted a positive index for patients' overall survival. What is more, overexpression of TRIM26 significantly suppressed NSCLC cell growth. Our further studies indicated that overexpression of TRIM26 inhibited the phosphorylation of PI3K p85 and AKT. And overexpressed TRIM26 regulated cell cycle-related genes' expression, including downregulating CDK4, Cyclin A, Cyclin D1, Cyclin D3, and Cyclin E, and upregulating p27 expression. Finally, we found that TRIM26 up-regulated PTEN expression by stabilizing PTEN protein in NSCLC cells. Collectively, our present study indicated that TRIM26 was decreased in NSCLC and overexpression of TRIM26 inhibited NSCLC cell growth by suppressing PI3K/AKT pathway, which suggested that TRIM26 could be as a potential target for the treatment of NSCLC in the future.

Keywords: AKT; PTEN; TRIM26; cell growth; non-small cell lung cancer.

MeSH terms

  • A549 Cells
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Class Ia Phosphatidylinositol 3-Kinase / genetics
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism
  • Cyclin A / genetics
  • Cyclin A / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin D3 / genetics
  • Cyclin D3 / metabolism
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Survival Analysis
  • Tripartite Motif Proteins / genetics*
  • Tripartite Motif Proteins / metabolism
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • CCND1 protein, human
  • CCND3 protein, human
  • Cyclin A
  • Cyclin D3
  • Cyclin E
  • Tripartite Motif Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • TRIM26 protein, human
  • Ubiquitin-Protein Ligases
  • Class Ia Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • PTEN Phosphohydrolase
  • PTEN protein, human