Dataset Information

Deduction of novel genes potentially involved in hypoxic AC16 human cardiomyocytes using next-generation sequencing and bioinformatics approaches.

ABSTRACT: Atherosclerotic cardiovascular disease and acute myocardial infarction are the leading causes of mortality worldwide, and apoptosis is the major pathway of cardiomyocyte death under hypoxic conditions. Although studies have reported changes in the expression of certain pro?apoptotic and anti?apoptotic genes in hypoxic cardiomyocytes, genetic regulations are complex in human cardiomyocytes and there is much that remains to be fully elucidated. The present study aimed to identify differentially expressed genes in hypoxic human AC16 cardiomyocytes using next?generation sequencing and bioinformatics. A total of 24 genes (15 upregulated and 9 downregulated) with potential micro (mi)RNA?mRNA interactions were identified in the miRmap database. Utilising the Gene Expression Omnibus database of cardiac microvascular endothelial cells, tensin 1, B?cell lymphoma 2?interacting protein 3 like, and stanniocalcin 1 were found to be upregulated, and transferrin receptor and methyltransferase like 7A were found to be downregulated in response to hypoxia. Considering the results from miRmap, TargetScan and miRDB together, two potential miRNA?mRNA interactions were identified: hsa?miRNA (miR)?129?5p/CDC42EP3 and hsa?miR?330?3p/HELZ. These findings contribute important insights into possible novel diagnostic or therapeutic strategies for targeting cardiomyocytes under acute hypoxic stress in conditions, including acute myocardial infarction. The results of the present study also introduce an important novel approach in investigating acute hypoxic pathophysiology.

SUBMITTER: Lee WH

PROVIDER: S-EPMC6192719 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Deduction of novel genes potentially involved in hypoxic AC16 human cardiomyocytes using next-generation sequencing and bioinformatics approaches.

Lee Wen-Hsien WH Tsai Ming-Ju MJ Chang Wei-An WA Wu Ling-Yu LY Wang Han-Ying HY Chang Kuo-Feng KF Su Ho-Ming HM Kuo Po-Lin PL

International journal of molecular medicine 20180831 5

Atherosclerotic cardiovascular disease and acute myocardial infarction are the leading causes of mortality worldwide, and apoptosis is the major pathway of cardiomyocyte death under hypoxic conditions. Although studies have reported changes in the expression of certain pro‑apoptotic and anti‑apoptotic genes in hypoxic cardiomyocytes, genetic regulations are complex in human cardiomyocytes and there is much that remains to be fully elucidated. The present study aimed to identify differentially ex ...[more]

PMID: 30226555

Similar Datasets

Project description:MicroRNAs (miRNAs) are key post-transcriptional regulators that affect protein translation by targeting mRNAs. Their role in disease etiology and toxicity are well recognized. Given the rapid advancement of next-generation sequencing techniques, miRNA profiling has been increasingly conducted with RNA-seq, namely miRNA-seq. Analysis of miRNA-seq data requires several steps: (1) mapping the reads to miRBase, (2) considering mismatches during the hairpin alignment (windowing), and (3) counting the reads (quantification). The choice made in each step with respect to the parameter settings could affect miRNA quantification, differentially expressed miRNAs (DEMs) detection and novel miRNA identification. Furthermore, these parameters do not act in isolation and their joint effects impact miRNA-seq results and interpretation. In toxicogenomics, the variation associated with parameter setting should not overpower the treatment effect (such as the dose/time-dependent effect). In this study, four commonly used miRNA-seq analysis tools (i.e., miRDeep2, miRExpress, miRNAkey, sRNAbench) were comparatively evaluated with a standard toxicogenomics study design. We tested 30 different parameter settings on miRNA-seq data generated from thioacetamide-treated rat liver samples for three dose levels across four time points, followed by four normalization options. Because both miRExpress and miRNAkey yielded larger variation than that of the treatment effects across multiple parameter settings, our analyses mainly focused on the side-by-side comparison between miRDeep2 and sRNAbench. While the number of miRNAs detected by miRDeep2 was almost the subset of those detected by sRNAbench, the number of DEMs identified by both tools was comparable under the same parameter settings and normalization method. Change in the number of nucleotides out of the mature sequence in the hairpin alignment (window option) yielded the largest variation for miRNA quantification and DEMs detection. However, such a variation is relatively small compared to the treatment effect when the study focused on DEMs that are more critical to interpret the toxicological effect. While the normalization methods introduced a large variation in DEMs, toxic behavior of thioacetamide showed consistency in the trend of time-dose responses. Overall, miRDeep2 was found to be preferable over other choices when the window option allowed up to three nucleotides from both ends.

Dataset Information

Deduction of novel genes potentially involved in hypoxic AC16 human cardiomyocytes using next-generation sequencing and bioinformatics approaches.

Publications

Deduction of novel genes potentially involved in hypoxic AC16 human cardiomyocytes using next-generation sequencing and bioinformatics approaches.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets