Loss of TRIM44 promotes renal cell carcinoma progression by regulating K48-linked ubiquitination of vimentin

TL;DR

TRIM44 acts as a tumor suppressor in kidney cancer by breaking down a protein called vimentin, which could help in predicting and treating the disease.

Contribution

This study identifies TRIM44 as a tumor suppressor in ccRCC and reveals its mechanism of promoting vimentin degradation via K48-linked ubiquitination.

Findings

TRIM44 is significantly downregulated in ccRCC tissues and correlates with poor prognosis.

TRIM44 inhibits cancer cell migration, invasion, and proliferation in ccRCC.

TRIM44 promotes vimentin degradation through K48-linked ubiquitination.

Abstract

Tripartite motif-containing 44 (TRIM44), a member of the TRIM protein family, has emerged as a regulator in multiple cancer types, yet its functional role and molecular mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly characterized. Here, we identified TRIM44 as a tumor suppressor in ccRCC through integrated clinical and functional analyses. Clinically, TRIM44 expression was significantly downregulated in ccRCC tissues compared with adjacent normal tissues, and its reduced expression correlated with advanced tumor stage and poor patient prognosis. Functionally, gain-of-function and loss-of-function experiments demonstrated that TRIM44 potently inhibited ccRCC cell migration, invasion, and proliferation in vitro and in vivo. Mechanistically, TRIM44 directly interacts with vimentin. Importantly, we found that TRIM44 promotes K48-linked polyubiquitination of vimentin through its B-box domain, thereby targeting vimentin for proteasomal degradation. Collectively, our study establishes TRIM44 as a critical regulator of ccRCC progression through vimentin destabilization, highlighting its potential as both a prognostic biomarker and therapeutic target for ccRCC.

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