MicroRNA expression patterns in TPL2 cutaneous squamous cell carcinoma

<p>Skin cancer remains the most common type of cancer in the world, and of skin cancers, cutaneous squamous cell carcinoma (cSCC) is the second most common. cSCC derives from a mutated cell type in the outermost layer of the skin called keratinocytes. In this shift from normal to mutated keratinocytes, the tumor suppressor gene Tpl2 plays a large molecular role. In cSCC, there is an activation of receptor tyrosine kinases (RTKs) in the MAPK pathway, a cell signaling path that regulates signals involved in cell proliferation, survival, differentiation, and inflammation. Research demonstrates that Tpl2 knockout mouse models (Tpl2 -/-) are more prone to developing cSCC than wildtype models (Tpl2 +/+). Tpl2 -/- keratinocytes exhibit the same upregulated activation of RTKs in MAPK as observed in cSCC, even at a baseline, though the reason for this is unknown. miRNAs, capable of downregulating protein expression, and dysregulated in many cancers, were considered as a possible reason. Specific miRNAs have been shown to regulate a family of receptors in MAPK called ERBB in breast cancer, but their role in cSCC is less studied. Therefore, it was hypothesized that miRNAs 7, 21, 205, and 125 could be differentially expressed between Tpl2 +/+ and Tpl2 -/- keratinocytes, and thus, involved in RTK upregulation in Tpl2 -/-. To study this, Tpl2 +/+ and Tpl2 -/- keratinocytes were isolated, RT-qPCR was utilized to assess miRNA abundance, and western blotting to quantify protein levels of RTKs. It was found that miR205 and miR21 are upregulated in Tpl2 -/- untreated keratinocytes. miR21’s upregulation was expected, but its role as an oncomiR should be further investigated. miR205’s upregulation was unexpected but could be explained by expression patterns in cSCC tumor samples in conjunction with Tpl2 baseline keratinocytes. It does not seem that these miRNAs are responsible for RTK activation, therefore, investigating Tpl2 -/- protein stability could be a potential future direction.</p>