TRIM8: Making the Right Decision between the Oncogene and Tumour Suppressor Role

Caratozzolo, Mariano Francesco; Marzano, Flaviana; Mastropasqua, Francesca; Sbisà, Elisabetta; Tullo, Apollonia

doi:10.3390/genes8120354

Cited by 29 publications

(26 citation statements)

References 94 publications

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“…Indeed, TRIM19/PML has been found to contribute to p53-mediated cell cycle arrest, apoptosis, and senescence [37] . Other members of the TRIM family linked to p53 action include TRIM8 [38] and TRIM29 [39] . Interestingly, TRIM16 is upregulated by the mutant p53-reactivating compound PK11007 in HCC1143 breast cancer cells [30] .…”

Section: Discussionmentioning

confidence: 99%

The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells

Synnott

Madden

Bykov

et al. 2018

Translational Oncology

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TP53 is the most frequently mutated gene in human cancer and thus an attractive target for novel cancer therapy. Several compounds that can reactive mutant p53 protein have been identified. APR-246 is currently being tested in a phase II clinical trial in high-grade serous ovarian cancer. We have used RNA-seq analysis to study the effects of APR-246 on gene expression in human breast cancer cell lines. Although the effect of APR-246 on gene expression was largely cell line dependent, six genes were upregulated across all three cell lines studied, i.e., TRIM16, SLC7A11, TXNRD1, SRXN1, LOC344887, and SLC7A11-AS1. We did not detect upregulation of canonical p53 target genes such as CDKN1A (p21), 14-3-3σ, BBC3 (PUMA), and PMAIP1 (NOXA) by RNA-seq, but these genes were induced according to analysis by qPCR. Gene ontology analysis showed that APR-246 induced changes in pathways such as response to oxidative stress, gene expression, cell proliferation, response to nitrosative stress, and the glutathione biosynthesis process. Our results are consistent with the dual action of APR-246, i.e., reactivation of mutant p53 and modulation of redox activity. SLC7A11, TRIM16, TXNRD1, and SRXN1 are potential new pharmacodynamic biomarkers for assessing the response to APR-246 in both preclinical and clinical studies.

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Section: Discussionmentioning

confidence: 99%

The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells

Synnott

Madden

Bykov

et al. 2018

Translational Oncology

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“…The HECT family has more than 30 members, whereas the RING family has more than 700 members most of which have not been studied [40,43]. TRIM8 is located on chromosome 10q24.3 and has a molecular weight of 61.5 kD [30]. The relationship between TRIM8 and cancer was observed for the rst time in glioblastoma [44].…”

Section: Discussionmentioning

confidence: 99%

“…Some TRIM family proteins are also involved in cancer development [29]. TRIM8 (Tripartite motif 8) is a RING nger family protein consisting of 551 amino acids, and is involved in the process of ubiquitination of proteins [30]. TRIM8 has dual, competing roles in cancers.…”

Section: Introductionmentioning

confidence: 99%

TRIM8 Inhibits Breast Cancer Proliferation by Regulating Estrogen Signaling

Tian

Tang

Liao

et al. 2020

Preprint

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Background: Breast cancer (BC) ranks first in female malignancies wordwide, 70% of which are estrogen receptor alpha (ERα) positive. Endocrine treatment, such as tamoxifen, is primary adjuvant therapy for patients with ER-positive BC, while some of them can develop acquired resistance during long-time treatment. Thus, further research on estrogen signaling is of significance to improve the prognosis of BC patients. Methods: In this study, we report that the E3 ubiquitin ligase TRIM8 acts as a novel regulator of ERα signaling. TRIM8 and ERα target genes expression levels were measured by RT-PCR, while protein expression levels were measured by western blot. CCK8 assay, clone formation, and EDU assay were used to measure cells proliferation. Wound healing assay was used to measure cells migration. Protein stability assay and protein ubiquitination analysis were used to detect ERα protein degradation. Co-immunoprecipitation assay was used to detect the interaction domain between TRIM8 and ERα. Results: TRIM8 is downregulated in BC and is associated with poor prognosis. The protein level of TRIM8 is negatively correlated with ERα. RNA-seq result revealed that estrogen signaling maybe a potential target of TRIM8. Knockdown of TRIM8 can significantly enhance BC cell proliferation and migration in vitro and in vivo. And this effect can be reversed by ERα depletion. Further mechanistic studies have shown that TRIM8 interacts with AF1 domain of ERα via its RING domain in the cytoplasm, and affects poly-ubiquitination of ERα protein. Conclusion: Our study reveals an interesting post-translational mechanism between ERα and TRIM8 in ER-positive BC, TRIM8 may be a potential therapeutic target for BC treatment.

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“…In addition, based on this risk model, we established a nomogram that can predict the five-, seven-, and 10-year survival rates of patients with KIRC. TRIM8, also known as RNF27 and GERP, is a highly conserved protein in the evolutionary process and is involved in a variety of biological processes, including carcinogenesis and inflammation 28 , and plays a vital role in innate immune pathway effects. In particular, TRIM8 regulates various signaling pathways through the direct interactions of key effectors, such as TAK1 29 , PIAS3 30 and SOCS-1 31 .…”

Section: Discussionmentioning

confidence: 99%

Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma

Wu¹,

Xu²,

Lin³

et al. 2020

Int. J. Med. Sci.

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Ubiquitination is presently a hot topic in the field of oncology. The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases, which play an essential role in the ubiquitination of proteins in the body. At the same time, research related to cancer stem cells (CSCs) is increasing in popularity in the field of oncology. CSCs are potentially chemically resistant and can be selectively enriched in patients receiving chemotherapy, ultimately leading to adverse outcomes, such as treatment failure and cancer recurrence. There is a close relationship between multiple TRIM family genes and CSCs. Accumulating evidence suggests that TRIM family proteins are expressed in diverse human cancers and act as regulators of oncoproteins or tumor suppressor proteins. In this study, we used biological information to explore the potential function of TRIM family genes related to CSCs in the development of pan-cancer. Kidney renal clear cell carcinoma (KIRC) is one of the deadliest malignant tumors in the world. Owing to its complex molecular and cellular heterogeneity, the effectiveness of existing KIRC-related risk prediction models is not satisfactory at present. Therefore, we focused on the potential role of these TRIM family genes in KIRC and used seven TRIM family genes to establish a prognostic risk model. This model includes TRIM16, TRIM32, TRIM24, TRIM8, TRIM27, PML, and TRIM11. In conclusion, this study provides further insight into the prognosis of KIRC, which may guide treatment.

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TRIM8: Making the Right Decision between the Oncogene and Tumour Suppressor Role

Cited by 29 publications

References 94 publications

The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells

The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells

TRIM8 Inhibits Breast Cancer Proliferation by Regulating Estrogen Signaling

Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma

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