Circular RNAs and their associations with breast cancer subtypes

Asha A. Nair, Nifang Niu, Xiaojia Tang, Kevin J. Thompson, Liewei M Wang, Jean-Pierre Kocher, Subbaya Subramanian, Krishna R Kalari

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Circular RNAs (circRNAs) are highly stable forms of non-coding RNAs with diverse biological functions. They are implicated in modulation of gene expression thus affecting various cellular and disease processes. Based on existing bioinformatics approaches, we developed a comprehensive workflow called Circ-Seq to identify and report expressed circRNAs. Circ-Seq also provides informative genomic annotation along circRNA fused junctions thus allowing prioritization of circRNA candidates. We applied Circ-Seq first to RNA-sequence data from breast cancer cell lines and validated one of the large circRNAs identified. Circ-Seq was then applied to a larger cohort of breast cancer samples (n = 885) provided by The Cancer Genome Atlas (TCGA), including tumors and normal-adjacent tissue samples. Notably, circRNA results reveal that normal-adjacent tissues in estrogen receptor positive (ER+) subtype have relatively higher numbers of circRNAs than tumor samples in TCGA. Similar phenomenon of high circRNA numbers were observed in normal breastmammary tissues from the Genotype-Tissue Expression (GTEx) project. Finally, we observed that number of circRNAs in normal-adjacent samples of ER+ subtype is inversely correlated to the risk-of-relapse proliferation (ROR-P) score for proliferating genes, suggesting that circRNA frequency may be a marker for cell proliferation in breast cancer. The Circ-Seq workflow will function for both single and multi-threaded compute environments. We believe that Circ-Seq will be a valuable tool to identify circRNAs useful in the diagnosis and treatment of other cancers and complex diseases.

Original languageEnglish (US)
Pages (from-to)80967-80979
Number of pages13
JournalOncotarget
Volume7
Issue number49
DOIs
StatePublished - 2016

Fingerprint

Breast Neoplasms
Workflow
Atlases
Neoplasms
Genome
Untranslated RNA
Computational Biology
Estrogen Receptors
circular RNA
Genotype
Cell Proliferation
Gene Expression
Recurrence
Cell Line
Genes

Keywords

  • Breast cancer
  • Circ-seq
  • Circular RNA
  • Molecular subtypes
  • Proliferation

ASJC Scopus subject areas

  • Oncology

Cite this

Circular RNAs and their associations with breast cancer subtypes. / Nair, Asha A.; Niu, Nifang; Tang, Xiaojia; Thompson, Kevin J.; Wang, Liewei M; Kocher, Jean-Pierre; Subramanian, Subbaya; Kalari, Krishna R.

In: Oncotarget, Vol. 7, No. 49, 2016, p. 80967-80979.

Research output: Contribution to journalArticle

Nair, AA, Niu, N, Tang, X, Thompson, KJ, Wang, LM, Kocher, J-P, Subramanian, S & Kalari, KR 2016, 'Circular RNAs and their associations with breast cancer subtypes', Oncotarget, vol. 7, no. 49, pp. 80967-80979. https://doi.org/10.18632/oncotarget.13134
Nair, Asha A. ; Niu, Nifang ; Tang, Xiaojia ; Thompson, Kevin J. ; Wang, Liewei M ; Kocher, Jean-Pierre ; Subramanian, Subbaya ; Kalari, Krishna R. / Circular RNAs and their associations with breast cancer subtypes. In: Oncotarget. 2016 ; Vol. 7, No. 49. pp. 80967-80979.
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