Skin cancer continues to be one of the top leading causes of mortality in Qatar (Qatar Cancer Society, 2015). Central to the tumor microenvironment is the predominance of cancer-associated fibroblasts (CAFs) [1], whose correlation with skin tumor progression remains largely unknown [2-4]. Therefore, the current project aims to answer two main questions (Figure 1): (1) What is the role of miRNA, a non-coding RNA that regulate protein expression at the post-transcriptional level, in activating resident fibroblasts into CAFs during skin carcinogenesis? (2) To halt skin cancer progression, can we identify potential targets that would induce functional conversion of CAFs into normal fibroblasts? Answers to these questions will delineate a novel strategy in treating skin cancer, which includes “reprogramming” of CAFs into normal ones by identifying and subsequently altering expression of specific miRNAs. Focusing on these miRNAs as potential therapeutic targets will open new venues for future research in Qatar and the Region that may lead to better treatment strategies of solid tumors, including skin cancer.