Is the methyltransferase, ASH1L a therapeutic target for endocrine-related cancers?

One of the features of aging is the loss of sex hormones and in-turn the change in function of androgen and oestrogen nuclear receptors. Changes in the epigenetic co-regulators of the nuclear receptors during aging are known to play a role in many of the age-related diseases such as dementia, diabetes and cancer. Alternative splicing is a mechanism crucial for proteomic diversity. Recent advancements in the understanding of histone modifications (epigenetic) and RNA methylation (epitranscriptomic) role in alternative splicing regulation, not only in transcriptional and translational regulation has highlighted the need for continued progress in dissecting this complex process. Recently, histone modifications have been identified as guiding the RNA methyltransferase complex to nascent RNA molecules allowing m6A addition co-transcriptionally. This exciting study linked epigenetics playing crucial role in RNA methylation. Further understanding of factors that can influence the epigenetic changes that will lead to changes in RNA methylation in disease needs to be investigated. Additionally, the androgen receptor was shown to play a role in alternative splicing in the presence of androgen. Therefore, this project will investigate how histone modifications influence nuclear receptor transcriptional and alternative splicing regulation utilising prostate and breast cancer cell models. Techniques that will be utilised are RNA inteference, analysis of RNAseq and ATACseq data, cell culture, qPCR, protein detection (immunoblotting and immunohistochemistry), pharmacological inhibitors, phenotypic assays (proliferation, invasion, apoptosis).