Large-scale discovery of previously undetected microRNAs specific to human liver

Abstract

MicroRNAs (miRNAs) are crucial regulators of gene expression in normal development and cellular homeostasis. While miRNA repositories contain thousands of unique sequences, they primarily contain molecules that are conserved across several tissues, largely excluding lineage and tissue-specific miRNAs. By analyzing small non-coding RNA sequencing data for abundance and secondary RNA structure, we discovered 103 miRNA candidates previously undescribed in liver tissue. While expression of some of these unannotated sequences is restricted to non-malignant tissue, downregulation of most of the sequences was detected in liver tumors, indicating their importance in the maintenance of liver homeostasis. Furthermore, target prediction revealed the involvement of the unannotated miRNA candidates in fatty-acid metabolism and tissue regeneration, which are key pathways in liver biology. Here, we provide a comprehensive analysis of the undiscovered liver miRNA transcriptome, providing new resources for a deeper exploration of organ-specific biology and disease.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0148-4) contains supplementary material, which is available to authorized users.

miR-625-3p and lncRNA GAS5 in Liquid Biopsies for Predicting the Outcome of Malignant Pleural Mesothelioma Patients Treated with Neo-Adjuvant Chemotherapy and Surgery

“…Small RNA sequencing data from a cohort of 87 MPM samples processed by The Cancer Genome Atlas (TCGA) were obtained through the Genomic Data Commons (GDC) (, dbgap Project ID: 6208). All small RNA sequencing data that had been generated using the Illumina HiSeq2000 platform was processed according to a previously described pipeline [48,49]. Briefly, aligned sequencing reads (.bam files) retrieved from GDC were converted to unaligned reads (.fastq files) and trimmed based on Phred quality scores (≥20).…”

Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma

“…MicroRNAs (miRNAs) are frequently disrupted in many cancer types and are suitable candidates to be used as biomarkers (5). Recent large-scale sequencing has allowed for the discovery of novel miRNAs, which may have greater clinical utility than their well-characterized and widely-expressed counterparts (6)(7)(8). The presence of these overlooked miRNAs is explained by the lack of stable expression across different tissues and low-coverage techniques used in early studies (6)(7)(8).…”

Small Noncoding RNA Expression in Cancer

“…Therefore, cell lineage-and tissue-specific miRNAs, especially the less abundant species, may not necessarily be included in current miR-Base annotations [55]. Re-analyses of high-throughput sequencing data of human tissues, cancers and cell lines have resulted in large scale discoveries of previously unannotated miRNAs that are expressed in a tissue-specific manner [55,[62][63][64].…”

“…A variety of statistical tests can be applied to determine differential expression. For example, tissue-specificity of the miRNAs derived from a given organ site can be assessed by comparing expression patterns across tissue types, by using Principal Component Analysis (PCA) or nonlinear t-Distributed Stochastic Neighbor Embedding (t-SNE) [62,63]. Additionally, differential expression of miRNA between biological states, such as neoplastic versus nonmalignant tissue samples, can be compared using various standard parametric or nonparametric statistical tests (Figure 3) [63,64].…”