Long non-coding RNAs are differentially expressed in dysferlinopathy (Preprint)
BACKGROUND Long non-coding RNAs (lncRNAs) are non-coding RNA transcripts greater than 200 nucleotides in length and are known to play a role in regulating the transcription of genes involved in vital cellular functions. We hypothesized the disease process in dysferlinopathy is linked to an aberrant expression of lncRNAs and mRNAs. OBJECTIVE In this study, we compared the lncRNA and mRNA expression profiles between the normal and dysferlin deficient murine myoblasts (C2C12 cells). METHODS LncRNA and mRNA expression profiling were performed using a microarray. Several lncRNAs with differential expression were validated using quantitative real time polymerase chain reaction (qRT-PCR). Gene Ontology analysis was performed to understand the functional role of the differentially expressed mRNAs. Further bioinformatics analysis was used to explore the potential function, lncRNA-mRNA correlation and potential targets of the differentially expressed lncRNAs. RESULTS We found 3195 lncRNAs and 1966 mRNAs that are differentially expressed. The chromosomal distribution of the differentially expressed lncRNAs and mRNAs was unequal, with the chromosome 2 having the highest number of lncRNAs and chromosome 7 having the highest number of mRNAs that were differentially expressed. Pathway analysis of the differentially expressed genes indicated the involvement of several signaling pathways including PI3K-Akt, FoxO, Wnt, cAMP and Hippo. The differentially expressed genes were also enriched for the GO terms, developmental process and muscle system process. Network analysis identified 8 statistically significant (p<0.05) network objects from the upregulated lncRNAs and 3 statistically significant network objects from the downregulated lncRNAs. CONCLUSIONS Our results thus far imply that dysferlinopathy is associated with an aberrant expression of multiple lncRNAs many of which may have a specific function in the disease process. GO terms and Network Analysis suggest a muscle specific role for these lncRNAs. To elucidate the specific roles of these abnormally expressed non-coding RNAs, further studies engineering their expression are required.