Evaluating miRNA Expression During Fibroblast Activation

Fibroblasts are the most prominent cell type residing in the stroma of solid tumors, including naïve fibroblasts (NF) and cancer-associated fibroblasts (CAF). NFs become activated in conditions requiring tissue remodeling, such as wound healing and fibrosis. As the wound-healing process completes, most of the myofibroblasts are removed by apoptosis. However, in the context of tumor progression, activated fibroblasts persist in the tissue and become one of the major contributors to tumorigenesis through numerous processes, including cell proliferation, angiogenesis, and repolarization of other pro-inflammatory cells.

Despite the recent optimism that CAFs represent a novel therapeutic target, the literature has been replete with clinical trial failures or even acceleration of cancer progression due to an inadequate understanding of the functions of CAF subpopulations in cancer progression 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. The presence of certain marker is not always directly correlated with certain phenotype and function of CAF subpopulation.

miRNAs are a class of non-coding RNAs that play an important role in regulating gene expression, which showed extensive deregulation in human cancers. The hierarchical clustering of the samples using miRNA expression levels resembled the developmental origins of the tissues and even partitioned tumors within a single lineage. With only a handful of studies evaluating miRNA expression in the context of fibroblasts, the project focuses on its potential of being indicative of tumor-promoting or tumor-suppressive activity of the cells, giving more insights into the differentiation of naïve fibroblasts into CAFs.