A comprehensive analysis of coding and non-coding transcriptomic changes in cutaneous squamous cell carcinoma

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  • Kunal Das Mahapatra, Karolinska Institutet
  • ,
  • Lorenzo Pasquali, Karolinska Institutet
  • ,
  • Jonas Nørskov Søndergaard, Karolinska Institutet
  • ,
  • Jan Lapins, Karolinska University Hospital, Stockholm
  • ,
  • István Balazs Nemeth, University of Szeged
  • ,
  • Eszter Baltás, University of Szeged
  • ,
  • Lajos Kemény, University of Szeged
  • ,
  • Bernhard Homey, Heinrich Heine University Düsseldorf
  • ,
  • Liviu Ionut Moldovan
  • Jørgen Kjems
  • Claudia Kutter, Karolinska Institutet
  • ,
  • Enikö Sonkoly, Karolinska Institutet, Karolinska University Hospital, Stockholm
  • ,
  • Lasse Sommer Kristensen
  • Andor Pivarcsi, Karolinska Institutet, University of Szeged

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression. To identify mRNAs, lncRNAs and circRNAs, which can be involved in cSCC, RNA-seq was performed on nine cSCCs and seven healthy skin samples. Representative transcripts were validated by NanoString nCounter assays using an extended cohort, which also included samples from pre-cancerous skin lesions (actinic keratosis). 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs were identified to be differentially expressed in cSCC. Targets of 519 transcription factors were enriched among differentially expressed genes, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were were identified to be dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel skin-enriched circRNAs, circ_IFFO2 and circ_POF1B, were identified and validated. In conclusion, a reference set of coding and non-coding transcripts were identified in cSCC, which may become potential therapeutic targets or biomarkers.

Original languageEnglish
Article number3637
JournalScientific Reports
Volume10
ISSN2045-2322
DOIs
Publication statusPublished - Dec 2020

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