Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.
The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA-induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute-1 (AGO1), argonaute-2 (AGO2), as well as double-stranded RNA-binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer.
Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany.
Michael
M
Sand
Marina
M
Skrygan
Dimitrios
D
Georgas
Christoph
C
Arenz
Thilo
T
Gambichler
Daniel
D
Sand
Peter
P
Altmeyer
Falk G
FG
Bechara
D000368:Aged; D060565:Argonaute Proteins / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055623:Keratosis, Actinic / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D034743:RNA-Induced Silencing Complex / Q000235:genetics; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*; D000099253:Trans-Activation Responsive RNA-Binding Protein
D060565:Argonaute Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D000099253:Trans-Activation Responsive RNA-Binding Protein; C474043:DGCR8 protein, human; C104647:PRKRA protein, human; C071598:TARBP1 protein, human