Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 17 April 2020 / Approved: 19 April 2020 / Online: 19 April 2020 (04:29:31 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Cancers 2020, 12, 1453
DOI: 10.3390/cancers12061453

Abstract

Background: DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B and HER2-positive Breast Cancer (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). Methods: To decipher its function, DSCAM-AS1 expression was measured by qRT-PCR in tissue samples from 93 BC patients in addition to a meta-analysis of 30 gene expression datasets, together with the evaluation of its association with clinical data. By computational analyses of our RNA-Seq in MCF-7 cells, we investigated the DSCAM-AS1 knock-down effects at both gene and isoform levels. Results: We confirmed DSCAM-AS1 overexpression in high grade Luminal A, B and HER2+ BCs and found a significant correlation with disease relapse. 908 genes were regulated by DSCAM-AS1-silencing, primarily involved in cell cycle and inflammatory response. Noteworthy, the analysis of alternative splicing and isoform regulation revealed 2,085 splicing events regulated by DSCAM-AS1, enriched in differential polyadenylation sites and 3’UTR shortening events. Finally, the DSCAM-AS1-interacting splicing factor hnRNPL was predicted as the most enriched RBP for exon skipping and 3’UTR events. Conclusion: 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.

Subject Areas

lncRNA; breast cancer; alternative splicing; estrogen receptor; RNA-Seq

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