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Principles of microRNA involvement in human cancers.

ABSTRACT: Naturally occurring microRNAs (miRNAs), small non-coding RNAs of 19 to 24 nucleotides (nt), are encoded in the genomes of invertebrates, vertebrates, and plants. miRNAs act as regulators of gene expression during development and differentiation at the transcriptional, posttranscriptional, and/or translational levels, although most target genes are still elusive. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In this review, we present principles related to the basic and translational research that has emerged in the last decade, a period that can be truly considered the "miRNA revolution" in molecular oncology. These principles include the regulation mechanism of miRNA expression, functions of miRNAs in cancers, diagnostic values and therapeutic potentials of miRNAs. Furthermore, we present a compendium of information about the main miRNAs that have been identified in the last several years as playing important roles in cancers. Also, we orient the reader to several additional reviews that may provide a deeper understanding of this new and exciting field of research.

SUBMITTER: Ling H

PROVIDER: S-EPMC4013296 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Principles of microRNA involvement in human cancers.

Ling Hui H Zhang Wei W Calin George A GA Calin George A GA

Chinese journal of cancer 20111101 11

Naturally occurring microRNAs (miRNAs), small non-coding RNAs of 19 to 24 nucleotides (nt), are encoded in the genomes of invertebrates, vertebrates, and plants. miRNAs act as regulators of gene expression during development and differentiation at the transcriptional, posttranscriptional, and/or translational levels, although most target genes are still elusive. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential pro ...[more]

PMID: 22035854

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Project description:The complex regulatory network between microRNAs and gene expression remains unclear domain of active research. We proposed to address in part this complex regulation with a novel approach for the genome-wide identification of biomodules derived from paired microRNA and mRNA profiles, which could reveal correlations associated with a complex network of de-regulation in human cancer. Two published expression datasets for 68 samples with 11 distinct types of epithelial cancers and 21 samples of normal tissues were used, containing microRNA expression (Lu et al. Nature Letters 2005) and gene expression (Ramaswarmy et al. PNAS 2001) profiles, respectively. As results, the microRNA expression used jointly with mRNA expression can provide better classifiers of epithelial cancers against normal epithelial tissue than either dataset alone (p=1×10(-10), F-Test). We identified a combination of six microRNA-mRNA biomodules that optimally classified epithelial cancers from normal epithelial tissue (total accuracy = 93.3%; 95% confidence intervals: 86% - 97%), using penalized logistic regression (PLR) algorithm and three-fold cross-validation. Three of these biomodules are individually sufficient to cluster epithelial cancers from normal tissue using mutual information distance. The biomodules contain 10 distinct microRNAs and 98 distinct genes, including well known tumor markers such as miR-15a, miR-30e, IRAK1, TGFBR2, DUSP16, CDC25B and PDCD2. In addition, there is a significant enrichment (Fisher's exact test p=3×10(-10)) between putative microRNA-target gene pairs reported in five microRNA target databases and the inversely correlated micro-RNA-mRNA pairs in the biomodules. Further, microRNAs and genes in the biomodules were found in abstracts mentioning epithelial cancers (Fisher Exact Test, unadjusted p<0.05). Taken together, these results strongly suggest that the discovered microRNA-mRNA biomodules correspond to regulatory mechanisms common to human epithelial cancer samples. In conclusion, we developed and evaluated a novel comprehensive method to systematically identify, on a genome scale, microRNA-mRNA expression biomodules common to distinct cancers of the same tissue. These biomodules also comprise novel microRNA and genes as well as an imputed regulatory network, which may accelerate the work of cancer biologists as large regulatory maps of cancers can be drawn efficiently for hypothesis generation.

Dataset Information

Principles of microRNA involvement in human cancers.

Publications

Principles of microRNA involvement in human cancers.

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