MiR‐625# and miR‐206 participate to the cellular response to matrix rigidity

Abstract

The extracellular matrix (ECM) affects many aspects of cell growth and behavior. Not only do cells respond to the composition of the ECM, but they also respond to its physical properties. In a seminal paper, Pelham and Wang observed that cells develop large integrin‐based adhesions on rigid surface, whereas on soft substrate adhesions remain immature and small. Since this cellular response to ECM stiffness is central in various aspects of biology, from physiology to disease, many efforts have been directed recently to understand how cells “sense” and respond to the stiffness of their environment. However this remains, so far, an open question. In this study, we investigated the role of micro RNAs (miRNAs) in the cellular response to matrix rigidity. Comparing miRNAs expression in fibroblast cultured on soft (1kPa) and stiff substrates (25kPa), we observed that ECM rigidity induced a decrease in miR‐625# and miR‐206 expression. Interestingly, inhibition of myosin II increased miR‐625# and miR‐206 expression, indicating that cell‐generated tension regulates miR‐206 and miR‐625# expression. Previous work have shown that fibronectin is a direct target of miR‐206, consistent with this we found that miR‐206 expression in cells cultured on stiff substrates decreased fibronectin expression. Additionally, we found that miR‐625# expression decreased cell spreading and survival on rigid ECM. These data indicate that miR‐206 and miR‐625# regulate the cellular response to ECM rigidity. We are currently pursuing this work to identify miR‐625# targets which impact cell adhesion and survival.