Dysregulated epigenetic enzymes and resultant abnormal epigenetic modifications (EMs) have been suggested to be closely related to tumor occurrence and progression. Histone modifications (HMs) can assist in maintaining genome stability, DNA repair, transcription, and chromatin modulation within breast cancer (BC) cells. In addition, HMs are reversible, dynamic processes involving the associations of different enzymes with molecular compounds. Abnormal HMs (e.g. histone methylation and histone acetylation) have been identified to be tightly related to BC occurrence and development, even though their underlying mechanisms remain largely unclear. EMs are reversible, and as a result, epigenetic enzymes have aroused wide attention as anti-tumor therapeutic targets. At present, treatments to restore aberrant EMs within BC cells have entered preclinical or clinical trials. In addition, no existing studies have comprehensively analyzed aberrant HMs within BC cells; in addition, HM-targeting BC treatments remain to be further investigated. Histone and non-histone protein methylation is becoming an attractive anti-tumor epigenetic therapeutic target; such methylation-related enzyme inhibitors are under development at present. Consequently, the present work focuses on summarizing relevant studies on HMs related to BC and the possible mechanisms associated with abnormal HMs. Additionally, we also aim to analyze existing therapeutic agents together with those drugs approved and tested through pre-clinical and clinical trials, to assess their roles in HMs. Moreover, epi-drugs that target HMT inhibitors and HDAC inhibitors should be tested in preclinical and clinical studies for the treatment of BC. Epi-drugs that target histone methylation (HMT inhibitors) and histone acetylation (HDAC inhibitors) have now entered clinical trials or are approved by the US Food and Drug Administration (FDA). Therefore, the review covers the difficulties in applying HM-targeting treatments in clinics and proposes feasible approaches for overcoming such difficulties and promoting their use in treating BC cases.
Background A normal umbilical cord has a single umbilical vein and two umbilical arteries. Single umbilical artery (SUA) is one of the most common umbilical anomaly detected by prenatal ultrasonography. The objective of this study was to evaluate the usefulness of copy number variation sequencing (CNV-seq) and standard karyotyping in fetuses with single umbilical artery (SUA) and to investigate the genetic etiology of prenatal SUA. Methods Data from pregnancies referred for invasive testing and copy number variation sequencing (CNV-seq) due to sonographic diagnosis of fetal with SUA from 2013 to 2022 were obtained retrospectively from the computerized database. The rates of chromosome aberrations and abnormal CNV-seq findings for isolated SUA, SUA accompanied with soft markers and ultrasound malformations were calculated. Results Of the 474 fetuses with SUA that underwent karyotyping, chromosomal abnormalities were detected in fetuses, with a chromosomal abnormality rate of 10.3% (49/474). The use of CNV-seq provides a 10.2% (18/177) incremental yield of detecting pathogenic CNVs in fetuses with SUA and normal karyotype. our study showed that the risk of pathogenic chromosomal abnormalities and copy number variations were increased in the SUA combined malformation or soft markers group compared to that in the isolated SUA group.Meanwhile, fetuses with isolated SUA had an additional 3.4% (6/177) of pathogenic CNVs on top of chromosome aneuploidies. Conclusion CNV-seq could aid in the risk assessment and genetic counseling in fetuses with isolated SUA, Integrating CNV analysis and karyotyping for prenatal diagnosis of SUA in prenatal diagnosis can provide more accurate genetic proof for prenatal counseling and prediction of fetal outcomes.
PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.
Aims: Vascular Calcification (VC) is recognized as an independent predictor of cardiovascular events. Estrogen replacement was reported as protective treatment against vascular calcification in postmenopausal women, while it is controversial because of its potential carcinogenicity. ERα co-regulators have been putatively considered as potential therapeutic targets for ERα-related cancers. However, the modulation of ERα action and biological function of ERα co-regulators in vascular calcification are still elusive. Methods and Results: KDM4B (Histone lysine demethylases 4B) was identified to be highly expressed in β-phosphoglycerol treated human and mouse aortic smooth muscle cells (ASMCs) and VitD3-overloaded mice during calcification by Western blot and immunofluorescence staining. Co-immunoprecipitation (Co-IP) and confocal immunofluorescence imaging were performed to show the association between KDM4B and ERa. Luciferase reporter assay demonstrated that KDM4B downregulated ERa-induced transactivation, and qPCR results showed that KDM4B depletion increased mRNA expression of endogenous ERa target gene; the results by co-IP showed that KDM4B associated with PRC2 complex and ERa. ChIP assay (Chromatin immunoprecipitation) demonstrated that KDM4B depletion decreased the recruitment of PRC2 (Polycomb repressive complex 2) complex to estrogen response element (ERE) regions, thereby down-regulating the level of H3K27me3. Finally, KDM4B-mediated enhancement of ASMCs calcification was attenuated by the estrogen treatment. Conclusion: KDM4B inhibits ERα-induced transactivation independent of its JmjC enzyme active region. KDM4B is involved in vascular calcification via down-regulation of ERα action. KDM4B associates with PRC2 complex to be recruited to ERE element of ERα downstream target gene, thereby modulating histone H3K27me3 modification on the ERE region, suggesting KDM4B acts as a new potential therapeutic target for VC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.