A bioinformatics approach for identification lncRNA-miRNA-protein interactions for SNHG1 and SNHG5

Abstract

BackgroundLong non-coding RNAs (lncRNAs) have regulatory effects on several biological molecules and interactions with mRNAs, miRNAs and proteins. Small nucleolar RNA host genes (SNHGs) are a group of these transcripts with accredited functions in the carcinogenesis process. MethodsWe applied three in silico methods for identification of the putative functions of SNHG1 and SNHG5 in breast cancer. In the first strategy, we used in silico tools to identify interaction between lncRNAs and miRNAs. Subsequently, we recognized shared transcription factors (TFs) between the lncRNAs and miRNAs and the miRNA targets. Finally, clustering analysis was used to identify the biological functions. In the second strategy, we analyzed co-expression pattern of these lncRNAs and mRNAs by using the results of high throughput studies. The third approach was based on assessment of interactions between lncRNAs and proteins. For this purpose, we used RPI-seq database which predicts these interactions through only sequence-derived data. Significance of interactions between lncRNAs and proteins was assessed through calculation of Random Forest (RF) and Support Vector Machine (SVM) classifiers. ResultsThe first strategy led to identification of hsa-miR-377-3p and hsa-miR-154-5p as two miRNAs that target both SNHG1 and SNHG5 and were down-regulated in breast cancer tissues. TFs that contribute in regulation of mentioned lncRNAs and miRNAs were also determined. EYA1, CREB1, TP63, SEMA4D, NR3C1 and AKT2 were determined as shared targets of mentioned miRNAs with cancer-related biological functions. The second strategy showed that SNHG1 is expected to modulate cell cycle progression and cell cycle checkpoints through regulation of expression of several genes. Third strategy showed that SNHG1 and SNHG5 had interactions with breast cancer-associated proteins such as HER2, ER, PR, BRCA1, BRCA2, PTEN, TNF, and p53. The interactions of SNHG1 with these proteins are predicted to be more prominent compared with SNHG5 interactions. ConclusionsThe current study highlighted the significant roles of SNHG1 and SNHG5 in the process of breast carcinogenesis which is possibly exerted through regulation of cancer-associated pathways and functional interactions with cancer-associated miRNAs, mRNAs and TFs.