MicroRNA-130a (miR-130a) regulates self-renewal capacity and tumor growth in cutaneous squamous cell carcinoma

Cutaneous Squamous Cell Carcinoma (cSCC) is a malignant neoplasm of epidermal keratinocytes resulting from the accumulation of somatic mutations in oncogenes and tumor suppressor genes due to solar radiation. MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein-coding genes at the posttranscriptional level. Previously, we performed a global analysis of miRNA expression in cSCC and identified miR-130a to be downregulated in tumors. 
However, its role in cSCC has been unknown. In this study, we investigated the function of miR-130a in cSCC using in vitro and in vivo models of cancer. qPCR results demonstrated the decreased expression of miR-130a in cSCC compared to healthy skin, which was also confirmed by in situ hybridization. The ectopic overexpression of miR-130a in two different SCC cell lines (A431 and UT-SCC-7) resulted in the suppression of their self-renewal capacity as determined by colony-forming assays. Moreover, miR-130a inhibited the migratory capacity of SCC cells as determined by scratch- and Transwell migration assays and their capacity to invade through Matrigel in Transwell invasion assays. To address the role of miR-130a in vivo, we engineered a stable miR-130a-overexpressing SCC cell line via lentiviral transduction and performed tumor xenograft experiments by injecting miR-130a-overexpressing cells as well as control cells into immunodeficient mice subcutaneously. Measurement of the tumor volume revealed that miR-130a suppressed cancer growth on mice from 4 weeks after injection and onwards significantly. The tumors were harvested at week 6 and we observed that tumors formed by miR-130a-overexpressing SCC cells weighed significantly less compared with controls. 
Taken together, miR-130a suppresses the self-renewal capacity and invasiveness in vitro and tumor growth in vivo in cSCC. Our results will contribute to the understanding of the molecular processes leading to the neoplastic transformation of keratinocytes.