Abstract
Cutaneous squamous cell carcinoma (cSCC) is a malignancy of epidermal keratinocytes that is responsible for approximately 20% of skin cancer-related death yearly. We have previously compared the microRNA (miRNA) expression profile of cSCC to healthy skin and found the dysregulation of miRNAs in human cSCC. In this study we show that miR-31 is overexpressed in cSCC (n = 68) compared to healthy skin (n = 34) and precancerous skin lesions (actinic keratosis, n = 12). LNA in situ hybridization revealed that miR-31 was specifically up-regulated in tumor cells. Mechanistic studies of inhibition of endogenous miR-31 in human metastatic cSCC cells revealed suppressed migration, invasion and colony forming ability, whereas overexpression of miR-31 induced these phenotypes. These results indicate that miR-31 regulates cancer-associated phenotypes of cSCC and identify miR-31 as a potential target for cSCC treatment.
Highlights
Cutaneous squamous cell carcinoma is the second most common skin cancer among fair-skinned people, with an increasing incidence over the last decades. cSCCs are associated with a substantial risk of metastasis and responsible for approximately 20% of skin cancer-related death yearly [1,2]. cSCCs can develop on precancerous lesions such as actinic keratosis (AK) or Bowen’s disease, and the risk to develop cSCCs is strongly associated with chronic sun exposure [3]
Up-regulation of miR-31 in skin squamous cell carcinoma Recently, we observed the deregulation of miRNA expression in cSCC and identified miR-31 as the most up-regulated miRNA in cSCC compared with healthy skin as determined by miRNA array [7]
To validate the array data and to explore the expression of miR-31 during skin cancer progression, we performed quantitative real-time PCR on a set of RNA isolated from freshfrozen skin biopsies obtained from healthy skin (n = 21), actinic keratosis (AK, pre-cancerous skin lesions, n = 12), and cSCCs (n = 13)
Summary
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer among fair-skinned people, with an increasing incidence over the last decades. cSCCs are associated with a substantial risk of metastasis and responsible for approximately 20% of skin cancer-related death yearly [1,2]. cSCCs can develop on precancerous lesions such as actinic keratosis (AK) or Bowen’s disease, and the risk to develop cSCCs is strongly associated with chronic sun (ultraviolet light) exposure [3]. Deregulation of miRNA expression has been observed in cancer, in which miRNAs can act as tumor suppressors or oncogenes depending on the tissue and the set of targets they regulate [9]. MiR-29 family members were shown to function as tumor suppressors and their downregulation being associated with the development and progression of several human malignancies including lung cancer, invasive breast cancer and hepatocellular carcinoma. MiR-21 functions as an oncogene and overexpression of this miRNA has been observed in most human malignancies and associated with important cancer hallmarks, such as uncontrolled cell proliferation, decreased apoptosis, invasion, and migration [10]. The survival of certain tumors can be completely dependent on the expression of specific oncogenic miRNAs (oncomiRs), for example, inactivation of miR21 or miR-155 in tumors overexpressing these miRNAs can lead to complete regression of these tumors in mice [12]. Restoration or silencing of cancer-associated miRNAs could lead to a favourable phenotype and may be used as a therapeutic approach in cSCC
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