Circular RNA expression in cutaneous squamous cell carcinoma.
BACKGROUND
CircularRNAs (circRNAs) are a reinvented class of abundant, stable, and evolutionary conserved non-coding RNAs with pivotal impacts on the cellular regulatory network and epigenetics by sequestering microRNAs (miRNAs) like a sponge.


OBJECTIVE
Purpose of the present study was to investigate circRNA expression in cutaneous squamous cell carcinoma (cSCC).


METHODS
A total of six cSCC and six non-lesional skin (control) biopsies were harvested. Microarray based circRNA expression was determined in the cSCC (n=3) and compared with the non-lesional skin (n=3) from a group of 13,617 distinct human circRNAs found in the Arraystar circRNA Array V2.0 (Arraystar, Rockville, USA). Microarray data were validated by quantitative real-time reverse transcription polymerase chain reaction in a separate group (cSCC, n=3 and non-lesional skin, n=3). miRNA binding to miRNA response elements (MREs) sequence data were acquired bioinformatically. Further data mining was performed to identify circRNAs containing MRE sequences that interacted with previously described miRNAs playing a role in cSCC formation.


RESULTS
A total of 322 circRNAs (143 up- and 179 down-regulated; fold change ≥2 and p<0.05) were identified as differentially expressed in cSCC. Furthermore, we identified a total of 1603 MREs that were part of the differentially expressed circRNAs. Among those circRNAs, a complementary MRE sequence was identified in 23 miRNAs previously known to be cSCC relevant.


CONCLUSIONS
This study showed that circRNAs are differentially expressed in cSCC and play an important role in tumor formation by interfering with cSCC relevant miRNAs through miRNA sequence complementary MREs participating in epigenetic control.
Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum 44791 Bochum, Germany; Department of Plastic Surgery, St. Josef Hospital, Catholic Clinics of the Ruhr Peninsula, 45257 Essen, Germany. Electronic address: michael.sand@ruhr-uni-bochum.de.
Michael
M
Sand
Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum 44791 Bochum, Germany.
Falk G
FG
Bechara
Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum 44791 Bochum, Germany.
Thilo
T
Gambichler
University of Michigan Kellogg Eye Center, Ann Arbor, MI 48105, USA.
Daniel
D
Sand
Department of Plastic Surgery, St. Josef Hospital, Catholic Clinics of the Ruhr Peninsula, 45257 Essen, Germany.
Michael
M
Bromba
Department of Internal Medicine, Knappschaftskrankenhaus University of Bochum, Zentrum für Klinische Forschung, Labor für Molekulare Gastroenterologische Onkologie, 44780 Bochum, Germany, Germany.
Stephan A
SA
Hahn
Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum 44791 Bochum, Germany.
Eggert
E
Stockfleth
Dermatologic Surgery Unit, Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum 44791 Bochum, Germany.
Schapoor
S
Hessam
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics*; D000079962:RNA, Circular; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D000079962:RNA, Circular; D012334:RNA, Neoplasm; D012313:RNA
CircularRNAs; Cutaneous squamous cell carcinoma; MicroRNAs; Non-coding RNAs