(A, B) qPCR and small-RNA-Seq independently validate downregulation of miR-203 and upregulation of miR-21 driven by oncogenic HrasG12V (n = 3 biological rep. qPCR, n = 2 small-RNA-Seq, mean ± SEM displayed, *p < 0.05, Student's t-test two-sided). (C) Gene track and quantification the 3′end of the miR-203 primary transcript based on 3Seq. (D) miR-203 primary transcript detection by qPCR (n = 3 biological replicates, Mean ± SEM displayed, *p < 0.05, ns = non-significant, Student's t-test two-sided). (E) miR-203 is downregulated in DMBA/TPA produced papillomas compared to normal adjacent tissue. Epi = epidermis, Der = dermis, T = tumor, and S = stroma. The black lines denote the epidermal/dermal and tumor/stroma boundary (F) miR-203 is downregulated in malignant SCCs derived from KrasG12D/Smad4cKO and passaged in immunocompromised mice. (G–O) Reduced miR-203 expression is correlated with increasing malignancy in human skin SCC cancers. Panels G, J, M were taken from regions with more histologically normal regions to demonstrate successful miR-203 hybridization. (P) miRNA-Seq quantification from patient matched normal and tumor tissue obtained from the TCGA consortium data (bar indicates mean value, Student's t-test two-sided). Scale bar = 50 μm.