The Potential Role of miRNAs in Fibroblast Activation

Fibroblasts are the most prominent cell type residing in the stroma of most solid tumors, which are present as naïve fibroblasts and cancer-associated fibroblasts. Naïve fibroblasts are normally inactivated, forming the stroma of tissues by synthesizing ECM components, such as collagens and fibronectin. They become activated in conditions requiring tissue remodelling, including wound healing and fibrosis. In the case of tumor, activated fibroblasts contribute to tumorigenesis, becoming cancer-associated fibroblasts (CAFs). However, the main challenge associated with targeting this unique population is their phenotypic and functional diversity in the TME, along with heterogeneity reflected in their origin. An extensive research was done on markers expressed by CAFs, unable to characterize subpopulations of CAFs due to lack of functional validation of the transcriptome and the expression of these markers by other cell lineages. The presence of certain marker is not always directly correlated with certain phenotype and function of CAF subpopulation. For this reason, this project aims to explore this unique population through changes in microRNA (miRNA) profile and to examine its potential to serve as an indicator of differentiation of fibroblasts into CAFs. It will examine if miRNA-21, -26b, -31 profiles of fibroblasts before and after interaction with cancer cells differ, in addition to whether miRNA expression can be informative of state of differentiation of fibroblasts. These findings will further help in exploring the requirement or suffiency of miRNAs for fibroblast activation and the possibility of characterizing this population through miRNA profiles.