ARID1 Proteins: from Transcriptional and Post-Translational Regulation to Carcinogenesis and Potential Therapeutics

Odnokoz, Olena; Wavelet-Vermuse, Cindy; Hophan, Shelby L; Bulun, Serdar E.; Wan, Yong

doi:10.2217/epi-2020-0414

Cited by 13 publications

(9 citation statements)

References 82 publications

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“…Cox regression analyses indicated that the risk score of the signature could be a powerful indicator of GC patient clinical outcome (Figures 7(e) and 7(f) ). Interestingly, TTN [ 21 ], TP53 [ 22 ], MUC16 [ 23 ], and ARID1A [ 24 ] were the top mutations in both cohorts and were involved in various biological processes. In addition, the frequencies of all mutated genes were higher in the high-risk group (96.74%) ( Figure 8(a) ) than in the low-risk group (84.75%) ( Figure 8(b) ), suggesting that somatic mutation was positively correlated with risk scores.…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and the Immune Microenvironment in Gastric Cancer

Wang

Chen

et al. 2021

BioMed Research International

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Ferroptosis is a mode of regulated cell death that depends on iron and plays pivotal roles in regulating various biological processes in human cancers. However, the role of ferroptosis in gastric cancer (GC) remains unclear. In our study, a total of 2721 differentially expressed genes (DEGs) were filtered based on The Cancer Genome Atlas (TCGA) ( n = 375 ) dataset. Weighted gene coexpression network (WGCNA) analysis was then used and identified 7 modules, of which the blue module with the most significant enrichment result was selected. By taking the intersections of the blue module and ferroptosis-related genes (FRGs), we obtained 23 common genes. Functional analysis was performed to explore the biological function of the genes of interest, and with univariate Cox regression (UCR) analysis, survival genes were screened to construct a prognostic model based on 3 genes (SLC1A5, ANGPTL4, and CGAS), which could play a role in predicting the survival of GC patients. UCR and multivariate Cox regression (MCR) analysis revealed that the prognostic index could be used as an independent prognostic indicator and validated using another GSE84437 dataset. Notably, patients in the high-risk group had higher mutation frequencies, such as TTN and TP53. TIMER analysis demonstrated that the risk score strongly correlated with macrophage and CD4+ T cell infiltration. In addition, the high- and low-risk groups illustrated different distributions of different immune statuses. Furthermore, the low-risk group had a higher immunophenoscore (IPS), which meant a better response to immune checkpoint inhibitors (ICIs). Finally, gene set enrichment analysis (GSEA) revealed several significant pathways involved in GC. In this study, a novel FRG signature was built that could predict GC prognosis and reflect the status of the tumor immune microenvironment.

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Section: Resultsmentioning

confidence: 99%

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and the Immune Microenvironment in Gastric Cancer

Wang

Chen

et al. 2021

BioMed Research International

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“…It has been reported that ARID1A in cancer can be regulated by way of promotor methylation or post-transcriptional modification. 15,41 In addition, there is also a report that ARID1A can be regulated by EBVencoded miRNA in EBV-positive GCs. 42 Due to the large number of the sample of this study, there are limitations in analyzing mutation and epigenetic profiles for every tumors; however, we expect that decreased ARID1A expression is associated with non-mutational alteration of ARI-D1A and results of this study support the supposition.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of ARID1A Expression Patterns Varies with Molecular Subtype in Advanced Gastric Cancer

et al. 2023

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Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC. The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods:We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns.Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC. Conclusions:Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.

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“…In some cases, post-translational changes lead to the loss of the ARID1A protein. Importantly, ARID1A inactivation is associated with poor outcomes and reduced chemosensitivity in many tumor types, including clear-cell OCs [2,377,383,[387][388][389].…”

Section: Arid1amentioning

confidence: 99%

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

Czegle

Huang

Soria

et al. 2023

Life

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There is an increasing understanding of the molecular and cytogenetic background of various tumors that helps us better conceptualize the pathogenesis of specific diseases. Additionally, in many cases, these molecular and cytogenetic alterations have diagnostic, prognostic, and/or therapeutic applications that are heavily used in clinical practice. Given that there is always room for improvement in cancer treatments and in cancer patient management, it is important to discover new therapeutic targets for affected individuals. In this review, we discuss mitochondrial changes in breast and gynecological (endometrial and ovarian) cancers. In addition, we review how the frequently altered genes in these diseases (BRCA1/2, HER2, PTEN, PIK3CA, CTNNB1, RAS, CTNNB1, FGFR, TP53, ARID1A, and TERT) affect the mitochondria, highlighting the possible associated individual therapeutic targets. With this approach, drugs targeting mitochondrial glucose or fatty acid metabolism, reactive oxygen species production, mitochondrial biogenesis, mtDNA transcription, mitophagy, or cell death pathways could provide further tailored treatment.

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ARID1 Proteins: from Transcriptional and Post-Translational Regulation to Carcinogenesis and Potential Therapeutics

Cited by 13 publications

References 82 publications

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and the Immune Microenvironment in Gastric Cancer

Development and Validation of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and the Immune Microenvironment in Gastric Cancer

Prognostic Significance of ARID1A Expression Patterns Varies with Molecular Subtype in Advanced Gastric Cancer

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

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