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

Abstract

The tripartite-motif (TRIM) family represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. TRIM family is involved in a variety of cellular signaling transductions and biological processes. TRIM family also contributes to cancer initiation, progress, and therapy resistance, exhibiting oncogenic and tumor-suppressive functions in different human cancer types. Moreover, TRIM family members have great potential to serve as biomarkers for cancer diagnosis and prognosis. In this review, we focus on the specific mechanisms of the participation of TRIM family members in tumorigenesis, and cancer development including interacting with dysregulated signaling pathways such as JAK/STAT, PI3K/AKT, TGF-β, NF-κB, Wnt/β-catenin, and p53 hub. In addition, many studies have demonstrated that the TRIM family are related to tumor resistance; modulate the epithelial–mesenchymal transition (EMT) process, and guarantee the acquisition of cancer stem cells (CSCs) phenotype. In the end, we havediscussed the potential of TRIM family members for cancer therapeutic targets.

Artificial miRNAs derived from miR‐181 family members have potential in cancer therapy due to an altered spectrum of target mRNAs

“…Among the significantly upregulated genes, the Tripartite Motif Containing 5 (TRIM5) gene exhibits the highest fold change of expression among all analyzed datasets. TRIM family members are known to be important drivers of cancer pathogenesis and drug resistance [36] and most importantly in cancer stem cell self‐renewal, probably by acting as cofactors for expression of pluripotency genes or suppressing differentiating markers [37]. Two other genes, namely Methionyl Aminopeptidase 2 ( METAP2 ) and Cyclin‐Dependent Kinase 2 associated protein 1 ( CDK2AP1 ), were also found to have a marked upregulated expression in glioblastoma TCGA data.…”

An AKT1-and TRIM21-mediated phosphodegron controls proteasomal degradation of HuR enabling cell survival under heat shock

“…TRIM21 overexpression also enhances cell proliferation and reduces apoptosis at physiological temperature, which conforms to reports of TRIM21’s potential tumorigenic role. 64 , 65 , 66 , 67 However, the role of TRIM21 in ensuring cell survival and proliferation in response to heat shock has not been shown before, and therefore expands the functional repertoire of TRIM21. Phosphorylation of S100 was found to be necessary for TRIM21 interaction with HuR and its subsequent degradation.…”

Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy

“…By regulating the quantity and quality of modified proteins, ubiquitination mediates almost all vital biological processes in eukaryotic cells, such as embryonic development, cell cycle control, and immunity [ 11 ]. If the ubiquitination process is abnormal, the disruption of protein homeostasis can ultimately lead to cellular dysfunction or even carcinogenesis [ 12 , 13 ]. Notably, studies indicate that ubiquitination is widely involved in the regulation of the TME [ 14 , 15 ].…”