BRD9 Inhibition by Natural Polyphenols Targets DNA Damage/Repair and Apoptosis in Human Colon Cancer Cells

Kapoor, Sudhir; Damiani, Elisabetta; Wang, Shan; Dharmanand, Ravirajan; Tripathi, Chakrapani; Perez, Jorge Enrique Tovar; Dashwood, Wan‐Mohaiza; Rajendran, Praveen

doi:10.3390/nu14204317

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…BRD9 is a bromodomain containing chromatin modifying protein. It is proved to play an important role in colon cancer ( Kapoor et al, 2022 ; Zhu et al, 2023 ). Interestingly, a recent study by Zhu et al, 2023 found that BRD9 is a critical regulator of glycolysis in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators

Liu,

Wang,

et al. 2023

Front. Pharmacol.

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Background: Colorectal adenocarcinoma (COAD) is a common malignant tumor with little effective prognostic markers. Cuproptosis is a newly discovered mode of cell death that may be related to epigenetic regulators. This study aimed to explore the association between epigenetic regulators and cuproptosis, and to establish a prognostic prediction model for COAD based on epigenetic regulators associated with cuproptosis (EACs).Methods: RNA sequencing data and clinical data of 524 COAD patients were obtained from the TCGA-COAD database, cuproptosis-related genes were from the FerrDb database, and epigenetic-related genes were from databases such as GO and EpiFactors. LASSO regression analysis and other methods were used to screen out epigenetic regulators associated with cuproptosis and prognosis. The risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Next, the survival difference, functional enrichment analyses, tumor mutation burden, chemotherapy drug sensitivity and other indicators between the two groups were compared and analyzed.Results: We found 716 epigenetic regulators closely related to cuproptosis, among which 35 genes were related to prognosis of COAD. We further screened out 7 EACs from the 35 EACs to construct a prognostic prediction model. We calculated the risk score of each patient based on these 7 genes, and divided the patients into high-risk group and low-risk group. We found that the overall survival rate and progression-free survival rate of the high-risk group were significantly lower than those of the low-risk group. This model showed good predictive ability in the training set, test set and overall data set. We also constructed a prognostic prediction model based on risk score and other clinical features, and drew the corresponding Nomogram. In addition, we found significant differences between the high-risk group and the low-risk group in tumor mutation burden, chemotherapy drug sensitivity and other clinical aspects.Conclusion: We established an effective predictive prediction model for COAD based on EACs, revealing the association between epigenetic regulators and cuproptosis in COAD. We hope that this model can not only facilitate the treatment decision of COAD patients, but also promote the research progress in the field of cuproptosis.

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Section: Discussionmentioning

confidence: 99%

An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators

Liu,

Wang,

et al. 2023

Front. Pharmacol.

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“…I-BRD9 also blocked colorectal adenocarcinoma tumor growth through a mechanism that involves the regulation of glycolytic gene expression by BRD9 [185]. Natural phenols that inhibit BRD9 as well as I-BRD9 reduced colon cancer cell viability and colony formation by increasing DNA damage and apoptosis [186]. I-BRD9 sensitized ovarian cancer cells to DNA damaging agents, synergizing with PARP inhibitors to suppress ovarian cancer tumor growth [63].…”

Section: Targeting Swi/snf Family VIII Bromodomainsmentioning

confidence: 99%

Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications

Dreier,

Walia,

de la Serna

2024

Epigenomes

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SWI/SNF enzymes are heterogeneous multi-subunit complexes that utilize the energy from ATP hydrolysis to remodel chromatin structure, facilitating transcription, DNA replication, and repair. In mammalian cells, distinct sub-complexes, including cBAF, ncBAF, and PBAF exhibit varying subunit compositions and have different genomic functions. Alterations in the SWI/SNF complex and sub-complex functions are a prominent feature in cancer, making them attractive targets for therapeutic intervention. Current strategies in cancer therapeutics involve the use of pharmacological agents designed to bind and disrupt the activity of SWI/SNF complexes or specific sub-complexes. Inhibitors targeting the catalytic subunits, SMARCA4/2, and small molecules binding SWI/SNF bromodomains are the primary approaches for suppressing SWI/SNF function. Proteolysis-targeting chimeras (PROTACs) were generated by the covalent linkage of the bromodomain or ATPase-binding ligand to an E3 ligase-binding moiety. This engineered connection promotes the degradation of specific SWI/SNF subunits, enhancing and extending the impact of this pharmacological intervention in some cases. Extensive preclinical studies have underscored the therapeutic potential of these drugs across diverse cancer types. Encouragingly, some of these agents have progressed from preclinical research to clinical trials, indicating a promising stride toward the development of effective cancer therapeutics targeting SWI/SNF complex and sub-complex functions.

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“…The literatures have been reported that BRD9 might be an important biomarker in colon cancer ( 15 , 16 ), while their studies little investigate the clinical significance of BRD9 in colorectal cancer. Our study intended to explore the clinical significance of BRD9 in colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Bromodomain-containing protein 9 activates proliferation and epithelial-mesenchymal transition of colorectal cancer via the estrogen pathway in vivo and in vitro

Chen¹,

Du²,

Chang³

et al. 2023

J Gastrointest Oncol

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Background: Bromodomain-containing protein 9 (BRD9) has been reported to be upregulated in multiple malignancies and facilitate cancer progression. However, there is a paucity of data relating to its expression and biological role in colorectal cancer (CRC). Therefore, this current study examined the prognostic role of BRD9 in CRC and the underlying mechanisms involved.Methods: Real-time polymerase chain reaction (PCR) and Western blotting were used to examine the expression of BRD9 in paired fresh CRC and para-tumor tissues from colectomy patients (n=31). Immunohistochemistry (IHC) was performed to assess BRD9 expression in 524 paraffin-embedded archived CRC samples. The clinical variables are including age, sex, carcinoembryonic antigen (CEA), location of tumor, T stage, N stage, and TNM classification. The effect of BRD9 on the prognosis of CRC patients was explored by Kaplan-Meier and Cox regression analyses. Cell counting kit 8 (CCK-8), clone formation assay, transwell assay, and flow cytometry were used to determine CRC cell proliferation, migration, invasion, and apoptosis, respectively. Xenograft models in nude mice were established to investigate the role of the BRD9 in vivo.Results: BRD9 mRNA and protein expression levels were significantly upregulated in CRC cells compared to normal colorectal epithelial cells (P<0.001). IHC analysis of 524 paraffin-embedded archived CRC tissues showed that high BRD9 expression was significantly associated with TNM classifications, CEA, and lymphatic invasion (P<0.01). Univariate and multivariate analyses indicated that BRD9 [hazard ratio (HR):

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BRD9 Inhibition by Natural Polyphenols Targets DNA Damage/Repair and Apoptosis in Human Colon Cancer Cells

Cited by 8 publications

References 48 publications

An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators

An effective prognostic model in colon adenocarcinoma composed of cuproptosis-related epigenetic regulators

Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications

Bromodomain-containing protein 9 activates proliferation and epithelial-mesenchymal transition of colorectal cancer via the estrogen pathway in vivo and in vitro

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