MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

Abstract

Actinic keratosis (AK) is a carcinoma in situ precursor of cutaneous squamous cell carcinoma (cSCC), the second most common cancer affecting the Caucasian population. AK is frequently present in the sun-exposed skin of the elderly population, UV radiation being the main cause of this cancer, and other risk factors contributing to AK incidence. The dysregulation of microRNAs (miRNAs) observed in different cancers leads to an improper expression of miRNA targets involved in several cellular pathways. The TaqMan Array Human MicroRNA Card assay for miRNA expression profiling was performed in pooled AK compared to healthy skin scraping samples from the same patients. Forty-three miRNAs were modulated in the AK samples. The expression of miR-19b (p < 0.05), -31, -34a (p < 0.001), -126, -146a (p < 0.01), -193b, and -222 (p < 0.05) was validated by RT-qPCR. The MirPath tool was used for MiRNA target prediction and enriched pathways. The top DIANA-mirPath pathways regulated by the targets of the 43 miRNAs are TGF-beta signaling, Proteoglycans in cancer, Pathways in cancer, and Adherens junction (7.30 × 10−10 < p < 1.84 × 10−8). Selected genes regulating the KEGG pathways, i.e., TP53, MDM2, CDKN1A, CDK6, and CCND1, were analyzed. MiRNAs modulated in AK regulate different pathways involved in tumorigenesis, indicating miRNA regulation as a critical step in keratinocyte cancer.

MicroRNA expression profiling of cutaneous squamous cell carcinomas and precursor lesions

“… 19 However, there have been limited studies performed in the setting of SCC or their precursor lesions such as AK and IEC. 20 , 21 Moreover, we still have very limited understanding on natural history of AK formation. Here, we performed a global miRNA expression profiling in SCC and its associated precursor lesions with the goal to find potential biomarkers and the role of miRNA in SCC development.…”

miRNAs: From Master Regulators of Gene Expression to Biomarkers Involved in Intercellular Communication

“…In their review, Nguyen et al [19] summarized how miR-29s can have opposite roles in different human cancers, acting as either oncogene or tumor suppressors. Chiantore et al [20] defined a miRNA signature in actinic keratosis, a skin condition that can lead to cancer, that may affect the pathways involved in tumor development. De Almeida et al [21] reported the most relevant findings on the epigenetic features of uterine leiomyosarcomas and endometrial stromal sarcoma, two rare and aggressive cancers.…”