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Article

DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3′-End Usage

1
Center for Molecular Systems Biology, University of Turin, Orbassano, 10043 Turin, Italy
2
Department of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, Italy
3
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
4
Department of Computer Science, University of Turin, 10149 Turin, Italy
5
Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS 3 Serenissima, Campo SS Giovanni e Paolo 6777, 30122 Venice, Italy
6
Department of Medical Sciences, University of Turin, 10126 Turin, Italy
7
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Turin, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(6), 1453; https://doi.org/10.3390/cancers12061453
Received: 7 April 2020 / Revised: 30 May 2020 / Accepted: 31 May 2020 / Published: 3 June 2020
DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B, and HER2-positive Breast Carcinoma (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). DSCAM-AS1 expression is analyzed in 30 public datasets and, additionally, by qRT-PCR in tumors from 93 BC patients, to uncover correlations with clinical data. Moreover, the effect of DSCAM-AS1 knockdown on gene expression and alternative splicing is studied by RNA-Seq in MCF-7 cells. We confirm DSCAM-AS1 overexpression in high grade Luminal A, B, and HER2+ BCs and find a significant correlation with disease relapse. In total, 908 genes are regulated by DSCAM-AS1-silencing, primarily involved in the cell cycle and inflammatory response. Noteworthily, the analysis of alternative splicing and isoform regulation reveals 2085 splicing events regulated by DSCAM-AS1, enriched in alternative polyadenylation sites, 3′UTR (untranslated region) shortening and exon skipping events. Finally, the DSCAM-AS1-interacting splicing factor heterogeneous nuclear ribonucleoprotein L (hnRNPL) is predicted as the most enriched RBP for exon skipping and 3′UTR events. The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer. View Full-Text
Keywords: lncRNA; breast cancer; alternative splicing; estrogen receptor; RNA-Seq lncRNA; breast cancer; alternative splicing; estrogen receptor; RNA-Seq
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MDPI and ACS Style

Elhasnaoui, J.; Miano, V.; Ferrero, G.; Doria, E.; Leon, A.E.; Fabricio, A.S.C.; Annaratone, L.; Castellano, I.; Sapino, A.; De Bortoli, M. DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3′-End Usage. Cancers 2020, 12, 1453. https://doi.org/10.3390/cancers12061453

AMA Style

Elhasnaoui J, Miano V, Ferrero G, Doria E, Leon AE, Fabricio ASC, Annaratone L, Castellano I, Sapino A, De Bortoli M. DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3′-End Usage. Cancers. 2020; 12(6):1453. https://doi.org/10.3390/cancers12061453

Chicago/Turabian Style

Elhasnaoui, Jamal, Valentina Miano, Giulio Ferrero, Elena Doria, Antonette E. Leon, Aline S.C. Fabricio, Laura Annaratone, Isabella Castellano, Anna Sapino, and Michele De Bortoli. 2020. "DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3′-End Usage" Cancers 12, no. 6: 1453. https://doi.org/10.3390/cancers12061453

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