Whole transcriptome analysis reveals non-coding RNA's competing endogenous gene pairs as novel form of motifs in serous ovarian cancer

The non-coding RNA (ncRNA) regulation appears to be associated to the diagnosis and targeted therapy of complex diseases. Motifs of non-coding RNAs and genes in the competing endogenous RNA (ceRNA) network would probably contribute to the accurate prediction of serous ovarian carcinoma (SOC). We conducted a microarray study profiling the whole transcriptomes of eight human SOCs and eight controls and constructed a ceRNA network including mRNAs, long ncRNAs, and circular RNAs (circRNAs). Novel form of motifs (mRNA-ncRNA-mRNA) were identified from the ceRNA network and defined as non-coding RNA's competing endogenous gene pairs (ceGPs), using a proposed method denoised individualized pair analysis of gene expression (deiPAGE). 18 cricRNA's ceGPs (cceGPs) were identified from multiple cohorts and were fused as an indicator (SOC index) for SOC discrimination, which carried a high predictive capacity in independent cohorts. SOC index was negatively correlated with the CD8+/CD4+ ratio in tumour-infiltration, reflecting the migration and growth of tumour cells in ovarian cancer progression. Moreover, most of the RNAs in SOC index were experimentally validated involved in ovarian cancer development. Our results elucidate the discriminative capability of SOC index and suggest that the novel competing endogenous motifs play important roles in expression regulation and could be potential target for investigating ovarian cancer mechanism or its therapy.

Automated summary

The regulation of non-coding RNA is associated with the diagnosis and targeted therapy of complex diseases. By constructing a ceRNA network and using a novel motif, SOC index was found to be negatively correlated with the CD8+/CD4+ ratio in tumor infiltration, reflecting the migration and growth of tumor cells in ovarian cancer progression.