Cutaneous squamous cell carcinoma (CSCC) is a common type of skin malignancy.,MicroRNA-221 (miRNA-221) is a critical non-coding RNA in tumor initiation and progression.,However, the molecular mechanisms of miRNA-221 in the development of CSCC remain unknown.,This study investigated the expression of miRNA-221 in CSCC and its potential tumor biological functions.,MTT assay, colony assay, PCR, and Western blot were adopted.,In this study, miRNA-221 expression was significantly higher in CSCC tissues and cell lines than in normal tissues and cells (P < 0.05).,Further functional experiments indicated that miRNA-221 knockdown inhibited the proliferation and cell cycle, while upregulation of miRNA-221 presented the opposite role.,The dual reporter gene assays indicated that PTEN is a direct target gene of miRNA-221.,PTEN protein or mRNA levels were decreased after the cells were transfected with miR-221 mimics.,Taken together, the obtained results indicated that miR-221 plays an oncogenic function in CSCC by targeting PTEN and further suggest that miR-221 may be a potential target for CSCC diagnosis and treatment.
Cutaneous squamous cell carcinoma (SCC) is the second most common human skin cancer with a rapidly increasing incidence among the Caucasian population.,Among the many regulators, responsible for cancer progression and growth, microRNAs (miRNA) are generally accepted as key players by now.,In our current study we found that microRNA-181a (miR-181a) shows low abundance in SCC compared to normal epidermal skin.,In vitro, miRNA downregulation in normal primary keratinocytes induced increased proliferation, while in vivo miR-181a downregulation in HaCaT normal keratinocytes showed tumor-like growth increase up to 50%.,Inversely, upregulation of these miRNAs in cancer cells lead to reduced cellular proliferation and induction of apoptosis in vitro.,An in vivo therapeutic model with induced miR-181a expression in SCC13 cancer cells reduced tumor formation in mice by 80%.,Modulation of miR-181a levels showed an inverse correlation with the proto-oncogene KRAS both on mRNA and protein level by direct interaction.,Knockdown of KRAS mimicked the anti-proliferative effects of miR-181a overexpression in patient-derived SCC cells and abolished the enhanced viability of HaCaT cells following miR-181a knockdown.,Furthermore, phospho-ERK levels correlated with KRAS levels, suggesting that the observed effects were mediated via the MAPK signaling pathway. miR-181a seemed regulated during keratinocyte differentiation probably in order to amplify the tumor suppressive character of differentiation.,Taken together, miR-181a plays a crucial tumor suppressive role in SCC by targeting KRAS and could be a promising candidate for a miRNA based therapy.