The mechanism of TRIM21 inhibiting the invasion and migration of ccRCC by stabilizing ASS1

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is characterized by its aggressive invasion and metastasis, posing significant clinical challenges. Understanding the molecular mechanisms underlying its progression is crucial for developing effective therapeutic strategies. The role of TRIM21 in regulating ASS1 in ccRCC addresses a critical gap in understanding the molecular mechanisms underlying ccRCC tumorigenesis. This study aims to investigate the role of TRIM21 in ccRCC and elucidate its expression patterns in clinical tissue and its impact on patient prognosis. The Real-time RT-PCR and western blot were used to determine the mRNA and protein expression of TRIM21 in ccRCC, and the TCGA database correlates with patient survival prognosis. Lentivirus-mediated TRIM21 modulation in ACHN, Caki-1, and 786-O cells reveals altered migration and invasion capabilities assessed via Wound Healing and Transwell assays. Metabolomic analysis reveals TRIM21 overexpression in ACHN cells induces metabolic reprogramming impacting urea cycle intermediates arginine, ornithine, and citrulline, elucidated via metabolomic detection kits. Our findings reveal that TRIM21 expression is low in ccRCC, but its high expression impedes cell migration and invasion while ameliorating urea cycle dysregulation by upregulating ASS1. Furthermore, TRIM21 enhances ASS1 protein stability through K63-linked ubiquitination modification. Moreover, clinical studies validating the prognostic value of TRIM21 and ASS1 in ccRCC patients may guide personalized treatment strategies ultimately improving patient outcomes. By investigating this interaction, researchers seek to shed light on potential diagnostic and therapeutic strategies for ccRCC offering valuable insights into its pathogenesis and metabolic reprogramming.

ORGANISM(S): Homo Sapiens

SUBMITTER: Qiao Zhang  

PROVIDER: PXD054847 | iProX | Tue Aug 13 00:00:00 BST 2024

REPOSITORIES: iProX