TRIM34 suppresses non-small-cell lung carcinoma via inducing mTORC1-dependent glucose utilization and promoting cellular death

Arch Biochem Biophys. 2024 Apr:754:109925. doi: 10.1016/j.abb.2024.109925. Epub 2024 Feb 7.

Abstract

Non-small-cell lung carcinoma (NSCLC) is a type of pernicious tumor, which owns high morbidity and mortality. TRIM34 has a stimulative role in cell apoptosis and a suppressive role in inflammation. However, no studies were focused on the regulatory impacts of TRIM34 in NSCLC. This study aimed to examine the underlying regulatory effects of TRIM34 in NSCLC. TRIM34 exhibited lower expression in NSCLC. TRIM34 facilitated mitochondrial damage and apoptosis in NSCLC. TRIM34 induced the increased activity of mTORC1 and accelerated glycolysis in NSCLC. Enhanced mitochondrial damage induced by TRIM34 overexpression was reversed after rapamycin (mTORC1 inhibitor) treatment in NSCLC. The strengthened cell apoptosis stimulated by TRIM34 overexpression was rescued after rapamycin treatment. TRIM34 activated mTORC1 to suppress NSCLC progression in vivo. TRIM34 suppressed NSCLC via inducing mTORC1-dependent glucose utilization and promoting cellular death. The results suggest that TRIM34 can be a useful therapeutic biomarker for NSCLC patients.

Keywords: Cell apoptosis; Glucose utilization; NSCLC; TRIM34; mTORC1.

MeSH terms

  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Glucose / metabolism
  • Humans
  • Lung Neoplasms* / pathology
  • Mechanistic Target of Rapamycin Complex 1
  • Signal Transduction
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • Glucose
  • Sirolimus
  • TRIM34 protein, human
  • Carrier Proteins