Regulating Mechanism Research Of Human Long Non-coding RNAs Associated Competing Triplets In Cancers

Transcripts without coding ability for proteins have been identified by large-scale genomic studies in recent years.These non-coding RNAs(ncRNAs)can be generally defined as small ncRNAs(< 200 nucleotides,including microRNAs,piRNAs,and siRNAs)and long non-coding(> 200 nucleotides,lncRNAs).MicroRNAs(miRNAs)have been involved in various complex diseases of human,including cancers.In contrast,regulating functions for a small number of human lncRNAs have been well characterized;these are studied to be associated with a wide range of complex functions,such as chromatin modification,regulation of cell apoptosis,cell invasion,stem cells reprogramming,and genomic imprinting.Recent studies have suggested that lncRNAs can interact with miRNAs and indirectly regulate mi RNA targets though competing interactions.However,the molecular mechanisms underlying these interactions are still largely unknown.In this study,we carried out systematic analysis of lncRNA,mi RNA and mRNA competing interactions,performed mi RNA target prioritization based on functional genomics data,and developed an integrated pipeline to identify active lncRNA-miRNA-gene interactions in cancers.Competing lncRNAs had sponge features distinct from non-competing lncRNAs.In the competing cross-talk network,disease-associated lncRNAs,miRNAs and mRNAs showed specific topological patterns indicative of their competence and control of communication within the network.Construction of global competing activity profile revealed that lncACTs had high specific activity.Based on the global cross-talk network,nine cancer-specific sub-networks were identified.H19-and BRCA1/2-associated lncACTs were able to discriminate between two different clinical outcomes in breast cancer.In summary,this study uncovered and systematically characterized global and sepcific properties of human lncACTs that may have prognostic value for predicting clinical outcome in cancer patients.