Dataset Information

Integrated miRNA-mRNA analysis in the habenula nuclei of mice intravenously self-administering nicotine.

ABSTRACT: A considerable amount of evidence suggests that microRNAs (miRNAs) play crucial roles in the neuroadaptation of drug addiction. Habenula (Hb), one of the critical brain regions involved in reward and addiction, can be divided into two anatomically and transcriptionally distinct regions: medial habenula (MHb) and lateral habenula (LHb) nuclei. However, very few studies have compared the functional roles of these regions. Here, by using mirConnX integrator and KEGG pathway mapping, we simultaneously analysed the differential expression patterns of miRNAs and messenger RNA (mRNA) within MHb and LHb under nicotine addiction. Significantly altered miRNAs and mRNAs were found in the Hb of mice intravenously self-administering nicotine. Interestingly, some miRNAs were oppositely regulated between the MHb and the LHb, and their potential targets included various genes of cell signalling pathways related to the degeneration of fasciculus retroflexus (FR). This study provides an improved insight into the differential regulation of habenular transcripts in nicotine addiction, as well as the potential functions of miRNAs in several biological pathways involved in the nicotine addiction.

SUBMITTER: Lee S

PROVIDER: S-EPMC4531287 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Integrated miRNA-mRNA analysis in the habenula nuclei of mice intravenously self-administering nicotine.

Lee Sangjoon S Woo Jiwan J Kim Yong Sik YS Im Heh-In HI

Scientific reports 20150811

A considerable amount of evidence suggests that microRNAs (miRNAs) play crucial roles in the neuroadaptation of drug addiction. Habenula (Hb), one of the critical brain regions involved in reward and addiction, can be divided into two anatomically and transcriptionally distinct regions: medial habenula (MHb) and lateral habenula (LHb) nuclei. However, very few studies have compared the functional roles of these regions. Here, by using mirConnX integrator and KEGG pathway mapping, we simultaneous ...[more]

PMID: 26260614

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Project description:Several studies have investigated miRNA and mRNA co-expression to identify regulatory networks at the transcriptional level. A typical finding of these studies is the presence of both negative and positive miRNA-mRNA correlations. Negative correlations are consistent with the expected, faster degradation of target mRNAs, whereas positive correlations denote the existence of feed-forward regulations mediated by transcription factors. Both mechanisms have been characterized at the molecular level, although comprehensive methods to represent miRNA-mRNA correlations are lacking. At present, genome-wide studies are able to assess the expression of more than 1000 mature miRNAs and more than 35,000 well-characterized human genes. Even if studies are generally restricted to a small subset of genes differentially expressed in specific diseases or experimental conditions, the number of potential correlations remains very high, and needs robust multivariate methods to be conveniently summarized by a small set of data.Nonparametric Kendall correlations were calculated between miRNAs and mRNAs differentially expressed in livers of patients with acute liver failure (ALF) using normal livers as controls. Spurious correlations due to the histopathological composition of samples were removed by partial correlations. Correlations were then transformed into distances and processed by multidimensional scaling (MDS) to map the miRNA and mRNA relationships. These showed: (a) a prominent displacement of miRNA and mRNA clusters in ALF livers, as compared to control livers, indicative of gene expression dysregulation; (b) a clustering of mRNAs consistent with their functional annotations [CYP450, transcription factors, complement, proliferation, HLA class II, monocytes/macrophages, T cells, T-NK cells and B cells], as well as a clustering of miRNAs with the same seed sequence; and (c) a tendency of miRNAs and mRNAs to populate distinct regions of the MDS plot. MDS also allowed to visualize the network of miRNA-mRNA target pairs.Different features of miRNA and mRNA relationships can be represented as thematic maps within the framework of MDS obtained from pairwise correlations. The symmetric distribution of positive and negative correlations between miRNA and mRNA expression suggests that miRNAs are involved in a complex bidirectional molecular network, including, but not limited to, the inhibitory regulation of miRNA targets.

Dataset Information

Integrated miRNA-mRNA analysis in the habenula nuclei of mice intravenously self-administering nicotine.

Publications

Integrated miRNA-mRNA analysis in the habenula nuclei of mice intravenously self-administering nicotine.

Similar Datasets

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