Publications by authors named "Pyoung-Hwa Park"
Article Synopsis
- The intestinal microbiota plays a crucial role in the development of colorectal cancer (CRC), possibly influencing DNA methylation.
- In a study of 203 CRC tumor cases, researchers found significant enrichment of specific bacteria (including those labeled "Superhigh") in CIMP-positive samples, indicating a potential link between gut bacteria and tumor characteristics.
- Using data from The Cancer Genome Atlas, the study demonstrated that these bacterial populations were associated with alterations in DNA methylation, suggesting that microbiota could be a factor in CRC progression through its influence on epigenetic changes.
In response to DNA double-strand breaks, MAD2L2-containing shieldin complex plays a critical role in the choice between homologous recombination (HR) and non-homologous end-joining (NHEJ)-mediated repair. Here we show that EZH2 inhibition upregulates MAD2L2 and sensitizes HR-proficient epithelial ovarian cancer (EOC) to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner. CARM1 promotes MAD2L2 silencing by driving the switch from the SWI/SNF complex to EZH2 through methylating the BAF155 subunit of the SWI/SNF complex on the MAD2L2 promoter.
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- Patients with BRCA1/2 mutations are more likely to develop certain types of cancers and now have treatment options like PARP inhibitors olaparib and rucaparib, which have been approved by the FDA.
- Resistance to these drugs poses a challenge, and this study explored mechanisms behind this resistance by creating resistant cell lines, discovering that changes in BRCA2 gene expression, rather than revert mutations, were linked to the resistance.
- Researchers identified DOT1L as a key player in the resistance mechanism, and silencing this gene could resensitize the cancer cells to olaparib, highlighting a potential pathway to overcome treatment challenges.
Inactivation of the subunits of SWI/SNF complex such as ARID1A is synthetically lethal with inhibition of EZH2 activity. However, mechanisms of de novo resistance to EZH2 inhibitors in cancers with inactivating SWI/SNF mutations are unknown. Here we show that the switch of the SWI/SNF catalytic subunits from SMARCA4 to SMARCA2 drives resistance to EZH2 inhibitors in ARID1A-mutated cells.
View Article and Find Full Text PDFARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers.
View Article and Find Full Text PDFCARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in human cancers. However, clinically applicable cancer therapeutic strategies based on CARM1 expression remain to be explored.
View Article and Find Full Text PDFARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored.
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