F1000Research | 2021
Regulatory landscapes of specific miRNAs are conserved between cell lines and primary tumors
Abstract
Background:\xa0MicroRNAs are essential gene expression regulators and play important roles in various biological processes, such as cancer. They have shown great translational promise as either diagnostic biomarkers or therapeutic targets. While the similarities between transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia have been thoroughly studied before, less is known on the microRNA side. This project aims to\xa0provide critical biological knowledge on the extent of consensus microRNA expression and regulation between cell line models and primary human tumors.\xa0 Method:\xa0First, we examined the similarity of miRNA expression profiles between CCLE cell lines and TCGA tumor samples for each cancer type. Next, we compared the expression of miRNAs associating the hallmarks of cancer pathways. Finally, we constructed miRNA-mRNA regulatory network for each cancer type and evaluated whether the regulatory role of each miRNA is conserved between cell lines and tumor samples.\xa0\xa0 Results:\xa0Our results indicate that, similar to gene expression, how well cancer cell line microRNA expression would capture the transcriptomic profile of human cancer tissues is greatly affected by the tumor type and purity. The cell-type composition for a cancer type also affects how accurately cancer cell lines could reflect the miRNA expression in tumor tissues. Furthermore, through network analysis, we show that certain microRNAs, not all, regulate the same set of target genes in both the cell line and human cancer tissues.\xa0 Conclusions:\xa0Through systematically comparing the miRNA expression profile and the regulatory network, our study highlights the biological differences between cell line and tumor samples and provides resources for future miRNA and cancer studies.