RT Journal Article
SR Electronic
T1 Discovering Competing Endogenous RNA Interactions in Breast Cancer Molecular Subtypes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 209015
DO 10.1101/209015
A1 Gulden Olgun
A1 Ozgur Sahin
A1 Oznur Tastan
YR 2017
UL http://biorxiv.org/content/early/2017/10/25/209015.abstract
AB Motivation Long non-coding RNAs(lncRNAs) can act as competing endogenous RNAs(ceRNAs); they indirectly regulate mRNAs expression levels by reducing the amount of microRNAs(miRNAs) available to target mRNAs. Previous work identified potential lncRNA-mediated ceRNA interactions in multiple cancer types including breast cancer. These ceRNA interactions have not been yet characterized for breast cancer subtypes.Results To find lncRNA-mediated ceRNA interactions in molecular subtypes of breast cancer, we use partial correlation analysis and kernel independence tests on patient gene expression profiles and further refine the candidate interactions with miRNA target information. We find that although there are sponges common to multiple subtypes, there are also distinct ceRNA regulatory interactions specific to certain subtypes. Furthermore, we show that functional enrichment of mRNAs involved in ceRNA interactions proposed roles of different biological processes for different subtypes. Interestingly, spatially proximal ceRNA interaction analysis suggested a tight regulation of HOX genes by HOTAIR using miR-196a-1 and miR-196a-2. We also discover subtype specific ceRNA interactions with high prognostic potential. When grouped based on the expression patterns of these sponge interactions, patients differ significantly in their survival distributions while patients groups based on individual RNA expression profiles of the sponge participants, the groups do not yield a significant difference in survival.Contact oznur.tastan{at}cs.bilkent.edu.tr