TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner

Abstract

Background Ubiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive. Methods RCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism. Results We identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications. Conclusions Our findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

“…TRIM37 is dysregulated in RCC, and its increased expression is associated with aggressive neoplastic phenotypes and poorer survival. Mechanistically, TRIM37 promotes the malignant progression of RCC via TGF-β1/SMAD signaling through its direct mediation by ubiquitinating-H2A modifications ( 31 ). Taken together, these findings indicate that TRIM proteins are associated with the occurrence and development of RCC and are potential biomarkers for prognostic prediction.…”

Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma

“…The study design and protocol were approved by the ethic committee of hospital. IHC staining was performed as previously described [ 32 , 33 ]. Briefly, the primary antibody was incubated as follows: anti-HNRNPC (Proteintech, 1: 200, China).…”

TRIM family contribute to tumorigenesis, cancer development, and drug resistance

“…A recent study also confirmed this conclusion in RCC tumors. Moreover, the upregulated expression of TRIM37 could predict aggressive neoplastic phenotypes [ 39 ]. In addition, knockdown of TRIM11 suppressed the tumorigenicity of chordoma cells [ 130 ].…”

“…TRIM47 also physically interacts with SMAD4, increasing its ubiquitination and degradation [ 215 ]. TRIM37 promotes RCC cell EMT and malignant progression through TGF-β signaling activation, as a consequence of TRIM37 mediated H2A ubiquitination modification [ 39 ]. TRIM59 was found to downregulate the protein expression of p-SMAD2 and thus inhibit the activity of the TGF-β signaling pathway [ 216 – 218 ].…”