Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Shi, Ying; Gong, Weihua; Gong, Xiangrong; Wang, Ping; Zhao, Xin

doi:10.1371/journal.pone.0241515

Cited by 7 publications

(8 citation statements)

References 42 publications

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“…In addition, this study assessed the correlation between GSDME and p-GP using the UALCAN dataset. Correlation analysis showed that tissues with higher GSDME expression had lower p-GP protein (Fig 2C) (R = −0.34, P <0.01), which was consistent with the results of previous research [31].…”

Section: Plos Onesupporting

confidence: 91%

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Promoting GSDME expression through DNA demethylation to increase chemosensitivity of breast cancer MCF-7 / Taxol cells

et al. 2023

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Objective Breast cancer is the most common and high-incidence cancer in women. It is mainly treated by surgery combined with chemoradiation. The main challenge in treating breast cancer patients is developing resistance to chemotherapeutics, so it is urgent to find potential strategies that can improve the chemotherapy effect of patients. In this study, we aimed to explore the role of GSDME methylation in the sensitivity of chemotherapy for breast cancer. Methods Here, we identified breast cancer MCF-7 / Taxol cells models using quantitative real-time PCR (qRT-PCR), Western blotting (WB), and cell counting kit-8 (CCK-8) analyses. Epigenetic changes in it were detected by Methylated DNA immunoprecipitation-sequencing and methylation-specific PCR. The expression level of GSDME in breast cancer cells was observed by qPCR and WB analyses. CCK-8 and colony formation assay were used to detect cell proliferation. Finally, pyroptosis was detected by LDH assay, flow cytometry, and WB analyses. Results Our results indicate that ABCB1 mRNA and p-GP expression are significantly increased in breast cancer MCF-7 / Taxol cells. GSDME enhancer methylation was found in drug-resistant cells and was associated with the down-regulation of GSDME expression. After treatment with decitabine (5-Aza-2’-deoxycytidine), the demethylation of GSDME induced the occurrence of pyroptosis and thereby inhibited the proliferation of MCF-7 / Taxol cells. We found that the upregulation of GSDME enhances the chemosensitivity of MCF-7 / Taxol cells to paclitaxel by inducing pyroptosis. Conclusion Taken together, we identified decitabine increases GSDME expression through DNA demethylation and induces pyroptosis, thus increasing the chemosensitivity of MCF-7 / Taxol cells to Taxol. Use of decitabine / GSDME / pyroptosis-based treatment strategies may be a new way to overcome the resistance of breast cancer to paclitaxel chemotherapy.

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Section: Plos Onesupporting

confidence: 91%

“…We used a low concentration gradient induction method to establish the Taxol-resistant MCF-7 /Taxol cells [31]. MCF-7 cells during logarithmic growth were seeded in a 25cm 2 six-well culture plates and cultured for 12h.…”

Section: Construction Of Taxol-resistant Cell Lines For Breast Cancermentioning

confidence: 99%

Promoting GSDME expression through DNA demethylation to increase chemosensitivity of breast cancer MCF-7 / Taxol cells

et al. 2023

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“…This phenomenon, by changing the expression of tumor suppressor or oncogenic genes and their promoters and/or enhancers, is involved in cancer initiation, progression, and even chemoresistance. In experimental models of breast cancer, exposure of MCF-7 cells to paclitaxel in a low-concentration gradient induction method (aimed at promoting chemoresistance) showed an overall increase in DNA methylation pattern ( Shi et al, 2020 ). To overcome this chemoresistance, the co-exposure of breast cancer cell lines to taxanes and phenethyl isothiocyanate (an epigenetic agent) was able to restore chemosensitivity ( Liu et al, 2013 ).…”

Section: Medical Properties Of Taxanesmentioning

confidence: 99%

Chemotherapeutic properties and side-effects associated with the clinical practice of terpene alkaloids: paclitaxel, docetaxel, and cabazitaxel

et al. 2023

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Over the years, many biological and synthetic agents have been explored and tested in attempts to halt the spread of cancer and/or cure it. Currently, several natural compounds have and are being considered in this regard. For example, paclitaxel is a potent anticancer drug that originates from the tree Taxus brevifolia. Paclitaxel has several derivatives, namely, docetaxel and cabazitaxel. These agents work by disrupting microtubule assembling dynamics and inducing cell cycle arrest at the G2/M phase of the cell cycle, ultimately triggering apoptosis. Such features have helped to establish paclitaxel as an authoritative therapeutic compound against neoplastic disorders. After the completion of compound (hemi) synthesis, this drug received approval for the treatment of solid tumors either alone or in combination with other agents. In this review, we explore the mechanisms of action of paclitaxel and its derivatives, the different formulations available, as well as the molecular pathways of cancer resistance, potential risks, and other therapeutic applications. In addition, the role of paclitaxel in hematological malignancies is explored, and potential limitations in the therapeutic use of paclitaxel at the clinical level are examined. Furthermore, paclitaxel is known to cause increased antigen presentation. The immunomodulatory potential of taxanes, alone or in combination with other pharmacologic agents, is explored. Despite terpene-alkaloids derivatives’ anti-mitotic potential, the impact of this class of drugs on other oncogenic pathways, such as epithelial-to-mesenchymal transition and the epigenetic modulation of the transcription profile of cancer cells, is also analyzed, shedding light on potential future chemotherapeutic approaches to cancer.

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“…MeDIP, coupled with massively parallel NGS, is a cost-effective method even suitable for minute clinical samples and has been demonstrated as an effective technique for methylation investigation [ 16 , 17 ]. Many cancer studies employed this technique to identify DMGs (Differentially Methylated Genes), such as breast cancer [ 18 ], ovarian cancer [ 19 ], pancreatic cancer [ 20 ], and others. In this study, we have analyzed the methylation profile of ovarian cancer samples using methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) by Illumina NextSeq 500 platform, which employs an anti-cytosine antibody resulting in the enrichment of methylated DNA.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive DNA methylation profiling by MeDIP-NGS identifies potential genes and pathways for epithelial ovarian cancer

Gautam,

Gupta,

Sachan

2024

J Ovarian Res

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Ovarian cancer, among all gynecologic malignancies, exhibits the highest incidence and mortality rate, primarily because it is often presents with non-specific or no symptoms during its early stages. For the advancement of Ovarian Cancer Diagnosis, it is crucial to identify the potential molecular signatures that could significantly differentiate between healthy and ovarian cancerous tissues and can be used further as a diagnostic biomarker for detecting ovarian cancer. In this study, we investigated the genome-wide methylation patterns in ovarian cancer patients using Methylated DNA Immunoprecipitation (MeDIP-Seq) followed by NGS. Identified differentially methylated regions (DMRs) were further validated by targeted bisulfite sequencing for CpG site-specific methylation profiles. Furthermore, expression validation of six genes by Quantitative Reverse Transcriptase-PCR was also performed. Out of total 120 differentially methylated genes (DMGs), 68 genes were hypermethylated, and 52 were hypomethylated in their promoter region. After analysis, we identified the top 6 hub genes, namely POLR3B, PLXND1, GIGYF2, STK4, BMP2 and CRKL. Interestingly we observed Non-CpG site methylation in the case of POLR3B and CRKL which was statistically significant in discriminating ovarian cancer samples from normal controls. The most significant pathways identified were focal adhesion, the MAPK signaling pathway, and the Ras signaling pathway. Expression analysis of hypermethylated genes was correlated with the downregulation of the genes. POLR3B and GIGYF2 turned out to be the novel genes associated with the carcinogenesis of EOC. Our study demonstrated that methylation profiling through MeDIP-sequencing has effectively identified six potential hub genes and pathways that might exacerbate our understanding of underlying molecular mechanisms of ovarian carcinogenesis.

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Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Cited by 7 publications

References 42 publications

Promoting GSDME expression through DNA demethylation to increase chemosensitivity of breast cancer MCF-7 / Taxol cells

Promoting GSDME expression through DNA demethylation to increase chemosensitivity of breast cancer MCF-7 / Taxol cells

Chemotherapeutic properties and side-effects associated with the clinical practice of terpene alkaloids: paclitaxel, docetaxel, and cabazitaxel

Comprehensive DNA methylation profiling by MeDIP-NGS identifies potential genes and pathways for epithelial ovarian cancer

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