TRIM9 (Tripartite Motif Containing 9)

Integrated analyses highlight TRIM9 as a tumor suppressor and prognostic biomarker, mediated via ubiquitination-dependent regulation of HNRNPU stability. This work provides insights into ubiquitination-driven PC pathogenesis and therapeutic targeting.

This review identifies TRIM proteins that are involved in urological cancers. Some of these proteins have the potential to be the therapeutic target.

The in vitro experiments revealed that the IC50 of XLW in UMCs was 63.21%, and the anti-UF effects of XLW may be closely associated with targets that inhibit cell proliferation and promote cell apoptosis by regulating TRIM9, NF-κB and p38MAPK expression. The integration of mass spectrometry, network pharmacology, molecular docking and biological experiments revealed the key constituents of XLW and its pharmacological mechanism in UFs, which may help in the discovery of therapeutic agents for treating UFs.

Sorafenib and lenvatinib are frontline treatments for advanced hepatocellular carcinoma (HCC). TRIM29 degrades YBX1 through ubiquitination, thereby inhibiting the PI3K/AKT signaling pathway and reversing lenvatinib resistance in HCC. TRIM29 can serve as an independent prognostic indicator of survival and recurrence in HCC patients, and it may provide new avenues for developing innovative treatment strategies for HCC.

Inhibiting TRIM9 caused a decrease in the IC50 of doxorubicin (DOX), and significant increases in the intracellular uptake, retention and absorption of DOX in HepG2/ADR cells. These findings may provide new insights into the mechanism of MDR development. The MDR-related hub genes, especially TRIM9 may be targeted therapeutically to enhance the prognosis of patients with drug-resistant HCC.

Mechanically, METTL14 was first found to activate miR-29c-3p through m6A and regulate tripartite motif containing 9 (TRIM9) to promote ubiquitination of pyruvate kinase isoform M2 (PKM2) and lead to its transition from tetramer to dimer, resulting in glucose metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to promote the progress of TNBC. Taken together, these findings reveal important roles of METTL14 in TNBC tumorigenesis and energy metabolism, which might represent a novel potential therapeutic target for TNBC.

TRIM9/67-IgG is a rare but likely high-risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086-1101.