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Open AccessArticle

The Circular RNA Landscape of Non-Small Cell Lung Cancer Cells

1
Division of Cancer Research, Department of Thoracic Surgery, Medical Center―University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
2
German Cancer Consortium (DKTK), Partner Site Freiburg, 79106 Freiburg, Germany
3
Division of RNA Biology & Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally.
Cancers 2020, 12(5), 1091; https://doi.org/10.3390/cancers12051091
Received: 30 March 2020 / Revised: 22 April 2020 / Accepted: 23 April 2020 / Published: 28 April 2020
The class of circular RNA (circRNA) is characterized by head-to-tail bonds between exons formed by backsplicing. Here, we provide a resource of circRNA expression in a comprehensive panel of 60 lung cancer and non-transformed cell lines (FL3C dataset). RNA sequencing after depletion of ribosomal RNA quantified the expression of circRNA and linear RNA. We detected 148,811 circular RNAs quantified by 2.8 million backsplicing reads originating from 12,251 genes. The number of identified circRNAs was markedly higher using rRNA depletion compared to public polyA-enriched RNA-seq datasets. CircRNAs almost never started in the first exon nor ended in the last exon and started more frequently in earlier exons. Most circRNAs showed high cell line specificity and correlated positively with their linear RNA counterpart. Known cancer genes produced more circRNAs than non-cancer genes. Subsets of circRNAs correlated with cell proliferation, histological subtype or genotype. CircTNFRSF21 was translated crossing the backsplice site in two different reading frames. Overexpression of circPVT1, circERBB2, circHIPK3, circCCNB1, circSMAD2, circTNFRSF21 and circKIF5B significantly increased colony formation. In conclusion, our data provide a comprehensive map of circRNA expression in lung cancer cells and global patterns of circRNA production as a useful resource for future research into lung cancer circRNAs. View Full-Text
Keywords: circular RNA; circRNA; NSCLC; lung cancer; lung adenocarcinoma circular RNA; circRNA; NSCLC; lung cancer; lung adenocarcinoma
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Van Der Steen, N.; Lyu, Y.; Hitzler, A.K.; Becker, A.C.; Seiler, J.; Diederichs, S. The Circular RNA Landscape of Non-Small Cell Lung Cancer Cells. Cancers 2020, 12, 1091.

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