TRIM8 Inhibits Breast Cancer Proliferation by Regulating Estrogen Signaling

Tian, Zelin; Tang, Jianing; Liao, Xing; Gong, Yan; Yang, Qian; Yun-xia, WU

doi:10.21203/rs.3.rs-42521/v1

Cited by 13 publications

(11 citation statements)

References 51 publications

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“…Furthermore, OTUD7B decreased the ERα ubiquitylation induced by the E3 ligase TRIM8 (Fig. 6F ) 33 . We further performed ubiquitination assay with a series of ubiquitin mutants to investigate which type of ubiquitin chain of ERα was deubiquitylated by OTUD7B.…”

Section: Resultsmentioning

confidence: 92%

OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation

Tang

Tian

et al. 2021

Cell Death Dis

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Breast cancer is the most common malignancy in women worldwide. Estrogen receptor α (ERα) is expressed in ∼70% of breast cancer cases and promotes estrogen-dependent cancer progression. In the present study, we identified OTU domain-containing 7B (OTUD7B), a deubiquitylase belonging to A20 subgroup of ovarian tumor protein superfamily, as a bona fide deubiquitylase of ERα in breast cancer. OTUD7B expression was found to be positively correlated with ERα in breast cancer and associated with poor prognosis. OTUD7B could interact with, deubiquitylate, and stabilize ERα in a deubiquitylation activity-dependent manner. Depletion of OTUD7B decreased ERα protein level, the expression of ERα target genes, and the activity of estrogen response element in breast cancer cells. In addition, OTUD7B depletion significantly decreased ERα-positive breast cancer cell proliferation and migration. Finally, overexpression of ERα could rescue the suppressive effect induced by OTUD7B depletion, suggesting that the ERα status was essential to the function of OTUD7B in breast carcinogenesis. In conclusion, our study revealed an interesting post-translational mechanism between ERα and OTUD7B in ERα-positive breast cancer. Targeting the OTUD7B–ERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer.

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Section: Resultsmentioning

confidence: 92%

OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation

Tang

Tian

et al. 2021

Cell Death Dis

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“…Various mechanisms have been proposed to elucidate endocrine resistance, including changes in ER regulators and diferent signaling pathways [25][26][27][28][29]. Posttranslational modifcations have been studied for their role in ERα signaling, among which ubiquitination of ERα is a crucial factor in endocrine insensitivity [6][7][8]30]. When ERα is stimulated with estrogen, it can be transferred to the nucleus and bind to cis-regulatory DNA region of target genes, promoting gene expression [31].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha

Zheng

Yang

et al. 2023

Journal of Oncology

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Breast cancer (BC) is the most common neoplastic and lethal malignancy in women. Although antiendocrine therapy is the main treatment for estrogen receptor alpha (ERα)-positive BC, the development of resistance is a major clinical complication. In this study, we aimed to explore the role of ubiquitin-specific peptidase 8 (USP8) in ERα signaling and identify potential targets for endocrine resistance. Public databases were used to analyze USP8 expression, prognosis, clinical characteristics, and immune cell infiltration. Immunohistochemistry and western blot assays were used to detect protein levels and ERα signaling. Quantitative reverse transcription-PCR was used to measure ERα target gene expression. The cell counting kit-8, wound-healing, clone formation, and Transwell assays were used to investigate the effects of USP8 depletion or inhibition on cell proliferation, migration, and invasion. An immunofluorescence assay was used for localizing USP8 and ERα, and a protein stability assay was performed for detecting the degradation of ERα protein. The cell cycle and apoptosis were assessed using flow cytometry. USP8 was highly expressed in the luminal subtype of BC and was associated with poor prognosis. The infiltration levels of many immune cells were positively correlated with USP8 expression. Depletion of USP8 dramatically decreased the ERα signaling activity and weakened the proliferation, migration, and invasion capabilities of BC cells. USP8 knockdown markedly induced apoptosis and cell cycle arrest ( G 0 / G 1 ). Colocalization analysis and protein stability assays indicated a probable mechanism by which USP8 regulates ERα. Our study demonstrates that USP8 might be crucial in BC development and may be considered a potential target for treating ER-positive BC malignancies in vitro.

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“…TRIM8, which performs both carcinogenic and antitumor activities in tumors, acts differently in tumors. Studies have shown that TRIM8 overexpression inhibits the proliferation and invasion of laryngeal squamous cell carcinoma and breast cancer ( 43 , 44 ). Caratozzolo et al.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of novel biomarker TRIM8 related to cervical cancer

Zhang

Dan²,

Ou³

et al. 2022

Front. Oncol.

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BackgroundCervical cancer, as a common gynecological disease, endangers female health. Give the lack of effective biomarkers for the diagnosis and treatment of cervical cancer, this paper aims to analyze the Gene Expression Omnibus (GEO) data sets using comprehensive bioinformatics tools, and to identify biomarkers associated with the cancer in patient samples.MethodsThe bioinformatics methods were used to extract genes related to cervical cancer from GSE39001, while the GEO2R online tool to elaborate on differentially expressed genes (DEGs) in normal and cancer samples, and to clarify related genes and functions. The results were verified by IHC, WB, CCK-8, clone formation and flow cytometry experiments.ResultsA total of 2,859 DEGs were identified in the GEO microarray dataset. We extracted genes associated with both ubiquitination and autophagy from the key modules of weighted gene co-expression network analysis (WGCNA), and the analysis showed that TRIM8 was of great significance for the diagnosis and prognosis of cervical cancer. Besides, experimental validation showed the high TRIM8 expression in cervical cancer, as well as its involvement in the proliferation of cervical cancer cells.ConclusionWe identified a biomarker (TRIM8) that may be related to cervical cancer through a series of analyses on the GEO dataset. Experimental verification confirmed the inhibition of cervical cancer cells proliferation by lowering TRIM8 expression. Therefore, TRIM8 can be adopted as a new biomarker of cervical cancer to develop new therapeutic targets.

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TRIM8 Inhibits Breast Cancer Proliferation by Regulating Estrogen Signaling

Cited by 13 publications

References 51 publications

OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation

OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation

Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha

Identification and validation of novel biomarker TRIM8 related to cervical cancer

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