The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma

Xie, Peiyi; Chen, Yanglin; Zhang, Hongfei; Zhou, Guichao; Chao, Qing; Wang, Jiangwen; Liu, Yue; Fang, Jiayu; Xie, Jing; Jing, Zhen; Wang, Zhiyuan; Hao, Lu; Huang, Da

doi:10.18632/aging.203293

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…For instance, the ‘writers’ METTL3 is upregulated and governs in invasion/migration through MMP2 in melanoma [ 35 ]. As for the ‘erasers’, ALKBH5 promotes the progression of uveal melanoma [ 36 ] and sensitizes tumors to cancer immunotherapy in melanoma [ 37 ]. Also, knockdown of FTO markedly improves cell sensitivity to interferon (IFN)-γ and anti-PD-1 therapeutics in melanoma, which suggested a promising anticarcinogenic therapy [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

Liu

Zhou

et al. 2021

Cancer Cell Int

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Background Melanoma is an extremely aggressive type of skin cancer and experiencing a expeditiously rising mortality in a current year. Exploring new potential prognostic biomarkers and therapeutic targets of melanoma are urgently needed. The ambition of this research was to identify genetic markers and assess prognostic performance of N6-methyladenosine (m6A) regulators in melanoma. Methods Gene expression data and corresponding clinical informations of melanoma patients as well as sequence data of normal controls are collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Quantitative real-time PCR (qRT-PCR) analysis was carried out to detect the RNA expression of IGF2BP3 in A375 cell line, melanoma tissues, and normal tissues. Western blot, cell proliferation, and migration assays were performed to assess the ability of IGF2BP3 in A375 cell line. Results Differently expressed m6A regulators between tumor samples and normal samples were analyzed. A three-gene prognostic signature including IGF2BP3, RBM15B, and METTL16 was constructed, and the risk score of this signature was identified to be an independent prognostic indicator for melanoma. In addition, IGF2BP3 was verified to promote melanoma cell proliferation and migration in vitro and associate with lymph node metastasis in clinical samples. Moreover, risk score and the expression of IGF2BP3 were positively associated with the infiltrating immune cells and these hub genes made excellent potential drug targets in melanoma. Conclusion We identified the genetic changes in m6A regulatory genes and constructed a three-gene risk signature with distinct prognostic value in melanoma. This research provided new insights into the epigenetic understanding of m6A regulators and novel therapeutic strategies in melanoma.

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Section: Discussionmentioning

confidence: 99%

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

Liu

Zhou

et al. 2021

Cancer Cell Int

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“…USP11 promotes colorectal cancer growth and metastasis by stabilizing PPP1CA, activating the ERK/MAPK pathway, and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) signaling ( 151 ), and interacting with nuclear factor 90 (NF90) to promote HCC proliferation and metastasis ( 152 ). OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, also promotes HCC proliferation and metastasis by regulating α-actinin 4 (ACTN4) ( 153 ). The deubiquitinating enzyme PSMD14 directly interacts with Snail and stabilizes it to promote cell migration and tumor metastasis of esophageal squamous cell carcinoma ( 154 ).…”

Section: Epigenetic In Tumor Progression and Metastasismentioning

confidence: 99%

Epigenetic modification regulates tumor progression and metastasis through EMT (Review)

et al. 2022

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Epigenetics is the study of heritable molecular determinants that are independent of phenotypic features. The epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling. In multicellular organisms, the epigenetic state of a cell is critical in determining its differentiation status and its ability to perform its proper function. These processes are now well recognized as being a substantial factor in tumor progression and metastasis. The process through which epithelial cells acquire mesenchymal features is known as epithelial-mesenchymal transition (EMT). EMT is associated with tumorigenesis, invasion, metastasis, and resistance to therapy in cancer. In the present review, we examine the recent studies that demonstrate the biological role of epigenetics, in particular, DNA methylation, histone modifications, non-coding RNAs, and chromatin remodeling in tumor progression and metastasis by regulating EMT status, and we provide an overview of the current state of knowledge regarding the epigenetics involvement in tumor progression and metastasis. Because epigenetic changes can be reversed, learning more about their biological roles in EMT will not only help us better understand how cancer progresses and spreads, but it will also help us identify new ways to diagnose and treat human malignancy which is currently lacking in the clinical setting.

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“…A growing number of reports suggest the role of OTUD3 in human cancers, such as breast cancer as well as lung cancer ( 35 , 46 ). Studies have demonstrated that OTUD3 is expressed in high amounts in HCC tissues and is associated with a poor prognosis in HCC patients ( 47 ). α-Actin 4 (ACTN4) is called an actin-binding protein and belongs to a family of actin-binding proteins.…”

Section: Ovarian Tumor Protease Otumentioning

confidence: 99%

“…α-Actin 4 (ACTN4) is called an actin-binding protein and belongs to a family of actin-binding proteins. OTUD3 can affect the expression of α-actin 4 (ACTN4) at the protein level and promote the proliferation, invasion, and metastasis of HCC by stabilizing ACTN4 by deubiquitination ( 47 ).…”

Section: Ovarian Tumor Protease Otumentioning

confidence: 99%

Research Progress of DUB Enzyme in Hepatocellular Carcinoma

et al. 2022

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According to GLOBOCAN 2021 cancer incidence and mortality statistics compiled by the International Agency for Research on Cancer, hepatocellular carcinoma (HCC) is the most common malignancy in the human liver and one of the leading causes of cancer death worldwide. Although there have been great advances in the treatment of HCC, such as regofenib, sorafenib, and lomvatinib, which have been developed and approved for the clinical treatment of advanced or metastatic HCC. However, they only prolong survival by a few months, and patients with advanced liver cancer are susceptible to tumor invasion metastasis and drug resistance. Ubiquitination modification is a type of post-translational modification of proteins. It can affect the physiological activity of cells by regulating the localization, stability and activity of proteins, such as: gene transcription, DNA damage signaling and other pathways. The reversible process of ubiquitination is called de-ubiquitination: it is the process of re-releasing ubiquitinated substrates with the participation of de-ubiquitinases (DUBs) and other active substances. There is growing evidence that many dysregulations of DUBs are associated with tumorigenesis. Although dysregulation of deuquitinase function is often found in HCC and other cancers, The mechanisms of action of many DUBs in HCC have not been elucidated. In this review, we focused on several deubiquitinases (DUBs) associated with hepatocellular carcinoma, including their structure, function, and relationship to hepatocellular carcinoma. hepatocellular carcinoma was highlighted, as well as the latest research reports. Among them, we focus on the USP family and OTU family which are more studied in the HCC. In addition, we discussed the prospects and significance of targeting DUBs as a new strategy for the treatment of hepatocellular carcinoma. It also briefly summarizes the research progress of some DUB-related small molecule inhibitors and their clinical application significance as a treatment for HCC in the future.

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The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma

Cited by 16 publications

References 23 publications

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

Epigenetic modification regulates tumor progression and metastasis through EMT (Review)

Research Progress of DUB Enzyme in Hepatocellular Carcinoma

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