What question did this study set out to answer?

This research aims to identify molecular targets impacting the prognosis of lung adenocarcinoma (LUAD).

March 28, 2026Open Access

TRIM31 inhibits ferroptosis in LUAD through facilitating ubiquitination and degradation of P53

Puntos clave

This research aims to identify molecular targets impacting the prognosis of lung adenocarcinoma (LUAD).
Analyzed gene data from The Cancer Genome Atlas (TCGA) for LUAD.
Identified hub genes using weighted gene co-expression network analysis (WGCNA).
Validated TRIM31 expression and its interaction with P53 through immunohistochemistry and co-immunoprecipitation.
Conducted loss-of-function assays to assess the role of TRIM31 in cell viability and ferroptosis.
TRIM31 expression correlated with advanced tumor stage and negatively with patient survival.
Knockdown of TRIM31 reduced cell viability and increased oxidative stress markers.
Experiments confirmed that TRIM31 promoted the ubiquitination and degradation of P53, affecting ferroptosis levels.

Resumen

Lung cancer (LC) causes large amount of cancer death worldwide. As the most common and aggressive type of LC, the molecular mechanisms in LUAD (Lung Adenocarcinoma) remain unclear. In order to find novel potential molecular targets for improving the prognosis of LUAD, we obtained gene information of LUAD patients from The Cancer Genome Atlas (TCGA) and identified hub genes through weighted gene co-expression network analysis (WGCNA). We selected the top 25% of total 5945 differently expressed genes (DEGs) and established 16 modules. The purple module was highly associated with tumor stage and chosen as key module. Further analysis revealed that the level of 6 hub genes (TRIM31, DKK1, FAM83A, RHOV, S100P and TSKU) were negatively relevant to survival rate but positively correlated with advanced tumor stage. Immunohistochemistry (IHC), western blot (WB) and reverse transcription-quantitative PCR (RT-qPCR) verified the high expression of TRIM31 in LUAD. Loss-of-function assays indicated TRIM31 accelerated viability, proliferation and metastasis of LUAD cells. According to the UbiBrowser website, TRIM31, as an E3 ubiquitin ligase, may be involved in the ubiquitination of P53, an important tumor suppressor. Co-immunoprecipitation verified the interaction between TRIM31 and P53. More importantly, the degradation rate of P53 was slowed when TRIM31 was knockdown. Further immunoblot assays revealed that TRIM31 promoted the ubiquitination and degradation of P53. P53 could inhibit the expression of SLC7A11 and was regarded as an important regulator of ferroptosis. Ferroptosis analysis showed that TRIM31 knockdown decreased cell viability and GSH, but increased ROS, MDA and iron, which could reverse by knockdown of P53. Above results displayed that TRIM31 effected ferroptosis level via P53. In addition, website prediction showed that BATF was a transcription factor of TRIM31, and experiments confirmed that BATF could indeed promote the transcription of TRIM31. Taken together, the data demonstrated that TRIM31 promoted LUAD progression by inhibiting ferroptosis via the TRIM31/P53/SLC7A11 axis.

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