Purpose: Osteosarcoma (OS) is one of the most prevalent primary malignant bone tumors in adolescent. HOTAIR is highly expressed and associated with the epigenetic modifications, especially DNA methylation, in cancer. However, the regulation mechanism between HOTAIR and DNA methylation and the biological effects of them in the pathogenesis of osteosarcoma remains elusive.
Method: Through RNA-sequencing and computational analysis, followed by a variety of experimental validations, we report a novel interplay between HOTAIR, miR-126, and DNA methylation in OS.
Results: We found that HOTAIR is highly expressed in OS cells and the knockdown of HOTAIR leads to the down-regulation of DNMT1, as well as the decrease of global DNA methylation level. RNA-sequencing analysis of HOTAIR-regulated gene shows that CDKN2A is significantly repressed by HOTAIR. A series of experiments show that HOTAIR represses the expression of CDKN2A through inhibiting the promoter activity of CDKN2A by DNA hypermethylation. Further evidence shows that HOTAIR activates the expression of DNMT1 through repressing miR-126, which is the negative regulator of DNMT1. Functionally, HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDKN2A axis.
Conclusion: These results not only enrich our understanding of the regulation relationship between non-coding RNA, DNA methylation, and gene expression, however, also provide a novel direction in developing more sophisticated therapeutic strategies for OS patients.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00432-017-2478-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bisphenol A alters JUN promoter methylation, impairing steroid metabolism in placental cells and linking to sub-representative phenotypes.
Gene
January 2025
School of Life Sciences, Fudan University, Shanghai 200433, China; MOE Engineering Research Center of Gene Technology, School of Life Sciences, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200433, China. Electronic address:
Bisphenol A (BPA) is a widely used industrial compound commonly found in various everyday plastic products. Known for its endocrine-disrupting properties, BPA can enter the human body through multiple pathways. Prenatal exposure to BPA not only disrupts placental structure and function but also interferes with normal steroid metabolism.
View Article and Find Full Text PDFDecoding the protein methylome: Identification, validation, and functional insights.
Bioorg Med Chem
December 2024
Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute for Drug Discovery, Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address:
Protein methylation regulates diverse cellular processes including gene expression and DNA repair. This review discusses the methods of identifying and validating substrates for protein methyltransferases (MTases), as well as the biological roles of methylation. Meanwhile, we outline continued efforts necessary to fully map MTase-substrate pairs and uncover the complex regulatory roles of protein methylation in cellular function.
View Article and Find Full Text PDFCharacterization of DNA methylation clock algorithms applied to diverse tissue types.
Aging (Albany NY)
January 2025
Department of Public Health Sciences, University of Chicago, Chicago, IL 60615, USA.
Background: DNA methylation (DNAm) data from human samples has been leveraged to develop "epigenetic clock" algorithms that predict age and other aging-related phenotypes. Some DNAm clocks were trained using DNAm obtained from blood cells, while other clocks were trained using data from diverse tissue/cell types. To assess how DNAm clocks perform across non-blood tissue types, we applied DNAm algorithms to DNAm data generated from 9 different human tissue types.
View Article and Find Full Text PDFTranscriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes.
BMC Mol Cell Biol
January 2025
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
Background: During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.
View Article and Find Full Text PDFExposure to childhood maltreatment is associated with specific epigenetic patterns in sperm.
Mol Psychiatry
January 2025
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, Turku, Finland.
Childhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the germ line. Here we investigated the associated between early life stress on the epigenome of sperm in humans with history of CME.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!