Genome-wide identification of lncRNAs and mRNAs differentially expressed in non-functioning pituitary adenoma and construction of an lncRNA-mRNA co-expression network

The involvement of long non-coding RNAs (lncRNAs) during tumorigenesis is a recent emerging theme. Yet no systematic evaluation of lncRNAs has been previously reported for non-functioning pituitary adenoma (NFPA), a fairly common type of intracranial tumor. Here, we report the first genome-wide expression profile for lncRNAs and mRNAs in NFPA, using formalin-fixed and paraffin-embedded tissue specimens. Using microarray analyses, we identified 113 lncRNAs and 80 mRNAs differentially expressed in NFPA; this list includes lncRNAs previously implicated in a variety of cancers. Using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) we further confirmed differential expression in NFPA for ten of the 113 lncRNAs. Using these ten doubly confirmed lncRNAs, we constructed an lncRNA-mRNA co-expression network comprising of 130 specific lncRNA-mRNA co-expression relationships. In addition, we conducted GO and KEGG analyses for the 80 mRNAs differentially expressed in NFPA. Our microarray and qRT-PCR analyses provided a working list of lncRNAs that may be functionally relevant to NFPA tumorigenesis. Our co-expression network in turn connected these largely uncharacterized lncRNAs to specific mRNAs, whose roles we further elucidated via GO and KEGG analyses, thus providing specific, testable hypotheses for the functions of these lncRNAs. Together, our study laid the foundation for future investigation of the specific function and mechanism by which lncRNAs are involved in NFPA tumorigenesis.
Summary statement: We identified long non-coding RNAs and mRNAs differentially expressed in non-functioning pituitary adenomas via microarray analyses, and provided working hypotheses for how these RNAs may function via co-expression network analyses.