Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression

MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated from the single miRNA hairpin precursor. However, current miRNA annotations lack comprehensive 5p-arm/3p-arm feature annotations. Among known human mature miRNAs, only half of them are annotated with arm features. This generated ambiguous results in many miRNA-Sequencing (miRNA-Seq) studies.

Here , researchers from Academia Sinica, Taipei have interrogated the TCGA (the Cancer Genome Atlas) miRNA expression datasets with an improved, fully annotated human 5p-arm and 3p-arm miRNA reference list. By utilizing this comprehensive miRNA arm-feature annotations, enhanced determinations and clear annotations were achieved for the miRNA isoforms (isomiRs) recognized from the sequencing reads. In the gastric cancer (STAD) dataset, as an example, 32 5p-arm/3p-arm 1799 specific miRNAs were found to be down-regulated and 24 5p-arm/3p-arm specific miRNAs were found to be up-regulated. The researchers have further extended miRNA biomarker discoveries to additional TCGA miRNA-Seq datasets and provided extensive expression information on 5p-arm/3p-arm miRNAs across multiple cancer types.


Volcano plot of combined miRNA expression and separate 5p-arm/3p-arm miRNA expression in TCGA (The Cancer Genome Atlas) gastric cancer tissues. miRNA expression data of TCGA stomach adenocarcinoma (STAD) were retrieved and re-analyzed using the comprehensive arm feature annotated miRNA list. The miRNA expression information of gastric cancer tissues is illustrated here by calculating the mean expression level from TCGA samples. Following analysis of variance (ANOVA) in the Partek software package, the volcano plot is displayed for selecting differentially expressed miRNA genes. (a) Precursor miRNAs gene loci expression by combining the 5p-arm and 3p-arm miRNAs together for analysis; (b) 5p-arm and 3p-arm miRNAs tabulated separately for their expression and analyzed.

Kuo WT, Su MW, Lee YL, Chen CH, Wu CW, Fang WL, Huang KH, Lin WC. (2015) Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets. J Clin Med 4(9):1798-814. [article]

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