Circular RNAs and their associations with breast cancer subtypes

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

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


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
Issue number49
StatePublished - 2016


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


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