- Hypoxia-mediated expansion of transcriptome due to epigenetic modifications in breast cancer tumorigenesis and chemoresistance:
- Role of deregulated epigenetic modifier in oral cancer:
- DNA methylation mediated regulation of PKM alternative splicing:
- Nutraceuticals mediated the effect of epigenetics in the restoration of normal isoform from cancer-specific splicing isoform in oral cancer:
Hypoxia-induced response plays a key role in the progression of Triple-negative breast cancer (TNBC) and is
considered as one of the hallmarks of TNBC. Hypoxia promotes an adaptive transcription response resulting in
epigenetic changes which support cancer cell growth. The epigenetic modifications are known to regulate
alternative splicing, which is an emerging hallmark of cancer. However, the interplay between hypoxia and
alternative splicing is largely unexplored in TNBC. Here, we want to investigate whether and how hypoxia
contributes to the generation of cancer-specific spliced isoforms via epigenetic modifications and whether
hypoxia-induced alternative splicing is involved in the tumorigenesis of TNBC.
Several studies have identified a change in epigenetic marks such as DNA methylation, histone modification, alterations in nucleosome remodeling, differential expression of miRNA, as well as altered expression of chromatin-modifying proteins in oral cancer. These epigenetic changes may lead to alteration in global gene expression pattern, which may attribute to the development and progression of oral cancers. Most of the studies focusing on epigenetic-based biomarkers have identified changes in DNA methylation, post-translational modifications of histones and miRNA pattern as biomarkers. However, chromatin-associated proteins which may contribute to these epigenetic changes have been largely ignored. Hence, we are investigating the deregulated expression of epigenetic modifiers in oral cancer. This study will help us in understanding the role of epigenetic events in cellular transformation and these epigenetic modifiers may serve as the markers for early-stage detection and prognosis of oral cancer.
Alternative splicing process can generate multiple protein coding isoforms and is the major source of transcriptome and proteome diversity. Aberrant spliced isoforms has been implicated in various cancers. Similarly deregulation of epigenetic modifications is also associated in the development and progression of many cancers. Here, our focus is to study the role of DNA methylation and DNA binding proteins in the regulation of PKM alternative splicing in breast cancer.
Nutraceuticals are natural products with nutrient value, reported to affect epigenetic modifiers and have substantial therapeutic effects on cancer. Here in this study, we investigate the use of epigenetic-based therapeutic compounds with minimal toxicity and side- effects (nutraceuticals) on cancer-specific alternative spliced isoform.