Functional prediction of long non-coding RNAs in ovarian cancer-Associated fibroblasts indicate a potential role in metastasis

Abstract

Cancer-Associated fibroblasts (CAFs) contribute to the poor prognosis of ovarian cancer. Unlike in tumour cells, DNA mutations are rare in CAFs, raising the likelihood of other mechanisms that regulate gene expression such as long non-coding RNAs (lncRNAs). We aimed to identify lncRNAs that contribute to the tumour-promoting phenotype of CAFs. RNA expression from 67 ovarian CAF samples and 10 normal ovarian fibroblast (NOF) samples were analysed to identify differentially expressed lncRNAs and a functional network was constructed to predict those CAF-specific lncRNAs involved in metastasis. Of the 1,970 lncRNAs available for analysis on the gene expression array used, 39 unique lncRNAs were identified as differentially expressed in CAFs versus NOFs. The predictive power of differentially expressed lncRNAs in distinguishing CAFs from NOFs were assessed using multiple multivariate models. Interrogation of known transcription factor-lncRNA interactions, transcription factor-gene interactions and construction of a context-specific interaction network identified multiple lncRNAs predicted to play a role in metastasis. We have identified novel lncRNAs in ovarian cancer that are differentially expressed in CAFs compared to NOFs and are predicted to contribute to the metastasis-promoting phenotype of CAFs.