Bioinformatics Seminars

Bioinformatics Seminar

Time: 11AM

6 September 2022

Network analysis of microRNA/transcription factor-driven cascade reveals the regulatory structure

Katherine Pillman
Centre for Cancer Biology (Uni SA)

Many biological systems are underpinned by key regulatory relationships between a microRNA and transcription factor pair. None more-so than in cancer, where much of the epithelial to mesenchymal transition (which plays an important role in cell invasiveness) hinges upon a negative feedback loop between the miR-200 microRNA and the ZEB1 transcription factor. It is well known that the switch from epithelial to mesenchymal cell state is triggered by repression of miR-200 levels followed by induction of ZEB1 expression and results in a huge cascade of gene expression changes. What is not well understood is the regulatory structure of the cascade; how many and which of these changes are effected directly through miR-200, or indirectly through ZEB1 or other regulators. Likewise, it is unclear how much of the cascade of changes occurs at the level of transcription or post-transcription. Gene correlation networks can identify clusters of co-expressed, and sometimes co-regulated genes. We have explored the structure of the miR/ZEB-activated regulatory cascade using a combination of linear modelling of gene expression and a network derived from a cell line model with a disabled regulatory circuit between the microRNA and transcription factor.

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