Maintaining the stability and integrity of the genome is critically essential for an organism’s survival. The molecular mechanisms that underpin genomic stability so far poorly understood. Retrotransposable elements, LINE-1 or L1, play an essential but undefined function in genome stability in particular breast cancer development. Recently, we initiated a study in breast cancers to discover mechanisms that underpin the role of L1 elements in cancer development. Given that genomic instability and altered expression of retrotransposon activity are intimately associated with many disease states, this research project will shed new light into how disease states arise and how the altered expression of L1 elements regulate this process.
Specific aims being investigated include
- Role of aberrant histone and DNA methylation in unchecked L1 activity in cancer cells
- Understand the regulatory role of endo-siRNAs and microRNAs pathways in global and gene-specific activation of L1 elements.
- Role of unchecked L1 activity in cancer cell proliferation.
- Explore the role of histones and DNA methylation machinery in cancer and tumour cell-lines.
- Defining the link between L1 activity and genomic stability in breast cancers.
Unravelling the relationship between small regulatory RNAi components and DNA methylation in the development of cancers may provide new strategies for future therapeutic and diagnostic approaches.