2. Academic Validation
  3. Effects of TRAF3 on the proliferation and migration of lung adenocarcinoma depend partly on pyroptosis

Effects of TRAF3 on the proliferation and migration of lung adenocarcinoma depend partly on pyroptosis

  • BMC Cancer. 2023 Oct 5;23(1):942. doi: 10.1186/s12885-023-11468-z.
Wangjia Wang 1 2,  Shiqi Wang 1,  Min Wang 1,  Yamei Ma 1,  Wanting Hu 1,  Binsha Wu 3,  Chichi Li 4,  Dan Zhang 5
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, 325000, China.
  • 2 Department of Rheumatism and Immunology, Shangyu People's Hospital, Shaoxing, 312300, China.
  • 3 Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, 325000, China.
  • 4 Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, 325000, China. [email protected].
  • 5 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, 325000, China. [email protected].
PMID: 37798663 DOI: 10.1186/s12885-023-11468-z
Abstract

Background: Tumor necrosis factor receptor-associated factor 3 (TRAF3) has specific regulatory effects on a wide range of diseases, including tumors. However, the effect and mechanism of TRAF3 on lung adenocarcinoma (LUAD) are still unknown. The aim of the present study was to make clear the role and potential mechanism of TRAF3 in LUAD.

Methods: TIMER2.0 database and western blot were applied to detect the expression of TRAF3 in lung adenocarcinoma tissue. Kaplan-Meier Plotter database was utilized to explore the effect of TRAF3 on the clinical prognosis of lung adenocarcinoma patients. Specific siRNA was used to inhibit the expression of TRAF3 in LUAD cells (A549 and H1299). CCK-8 and EdU assays were performed for assessing LUAD cells proliferation. Wound healing assay and transwell assay were performed for determining cells migration. CCK-8 assay was used to assess the response of the LUAD cells to paclitaxel. TIMER2.0 bioinformatics and western blot were employed to detect the effects of TRAF3 on Pyroptosis in LUAD.

Results: TRAF3 was highly expressed in lung adenocarcinoma tissues and cell lines. Patients with TRAF3 hyperexpression had a good prognosis compared to those with lower expression. TRAF3 inhibition notably induced proliferation and migration of LUAD cells. Inhibition of TRAF3 also weakened the sensitivity of LUAD cells to paclitaxel. Moreover, bioinformatics results showed that TRAF3 was positively correlated with the expression of pyroptosis-related genes in LUAD. Western blot assays showed that TRAF3 inhibition visibly decreased the expression of apoptosis-associated speck-like protein (ASC), cleaved Caspase-1 and matured- IL-1β.

Conclusions: Inhibition of TRAF3 promotes the proliferation and migration of LUAD cells, and reduces the sensitivity of LUAD cells to paclitaxel. The effects of TRAF3 on LUAD cells were mediated in part by caspase-1-dependent Pyroptosis.

Keywords

Lung adenocarcinoma (LUAD); Pyroptosis; Tumor necrosis factor receptor-associated factor 3 (TRAF3).

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