Multifaceted role of TRIM28 in health and disease

Abstract

The TRIM (tripartite motif) family, with TRIM28 as a key member, plays a vital role in regulating health and disease. TRIM28 contains various functional domains essential for transcriptional regulation, primarily through its interaction with KRAB-ZNF proteins, which influence chromatin remodeling and gene expression. Despite extensive research, the precise mechanisms by which TRIM28 impacts health and disease remain elusive. This review delves into TRIM28's multifaceted roles in maintaining health, contributing to a variety of diseases, and influencing cancer progression. In cancers, TRIM28 exhibits a dual nature, functioning as both a tumor promoter and suppressor depending on the cellular context and cancer type. The review also explores its critical involvement in processes such as DNA repair, cell cycle regulation, epithelial-to-mesenchymal transition, and the maintenance of stem cell properties. By uncovering TRIM28's complex roles across different cancers and other diseases, this review underscores its potential as a therapeutic target. The significance of TRIM28 as a versatile regulator opens the door to innovative therapeutic strategies, particularly in cancer treatment and the management of other diseases. Ongoing research into TRIM28 may yield key insights into disease progression and novel treatment options.

Keywords: DNA damage response; TRIM family; TRIM28; cancer pathogenesis; cancer therapy; transcriptional regulation.

FIGURE 1

Genes that interact with or are targets of TRIM28. This figure represents the interaction between TRIM28 and target genes, along with their effects, functions, and modifications, including polyubiquitination, deacetylation, and SUMOylation. This figure was created using BioRender and Microsoft Publisher 2016.

FIGURE 2

The expression level of TRIM28 across TCGA cancers. The TRIM28’s expression is upregulated in 21 cancers, while in three cancers, there is no significant change. This plot was extracted from UALCAN online database (https://ualcan.path.uab.edu/cgi‐bin/Pan‐cancer.pl?genenam=TRIM28). BLCA, bladder cancer; BRCA, breast cancer; CESC, cervical cancer; CHOL, bile duct cancer; COAD, colon cancer; ESCA, esophageal cancer; GBM, glioblastoma; HNSC, head and neck cancer; KICH, kidney chromophobe; KIRC, kidney clear cell carcinoma; KIRP, kidney papillary cell carcinoma; LIHC, liver cancer; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; PAAD, pancreatic cancer; PCPG, pheochromocytoma and paraganglioma; READ, rectal cancer; SARC, sarcoma; SKCM, melanoma; STAD, stomach cancer; THCA, thyroid cancer; THYM, thymoma; UCEC, endometrioid cancer.

FIGURE 3

TRIM28 signaling pathway and its corresponding effectors. This figure depicts the key proteins and pathways related to TRIM28 that are involved in cell proliferation, survival, genomic stability, and various cancer types. This figure was created using BioRender and Microsoft Publisher 2016.

FIGURE 4

TRIM28 in cancer therapy potential. The list of some cancers linked to TRIM28 treatment is visualized in this figure, emphasizing TRIM28’s function in therapeutic interventions, its potential as a target for therapeutic approaches, and the clinical results. This figure was created using BioRender and Microsoft Publisher 2016.