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Published on: May 19, 2019
Deduction of novel genes potentially involved in hypoxic AC16 human cardiomyocytes using next-generation sequencing
Wen-Hsien Lee1, Ming-Ju Tsai1, Wei-An Chang1
1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Insights
This study identified key gene expression changes in human heart cells under low oxygen conditions, revealing potential new targets for treating heart attacks and related diseases.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Genomics
Background:
- Atherosclerotic cardiovascular disease and acute myocardial infarction are leading global causes of death.
- Apoptosis is a primary mechanism of cardiomyocyte death during hypoxia.
- Genetic regulation of hypoxic cardiomyocyte response is complex and not fully understood.
Purpose of the Study:
- To identify differentially expressed genes in human cardiomyocytes under hypoxic conditions.
- To explore potential microRNA-mRNA interactions involved in the hypoxic response.
- To uncover novel diagnostic or therapeutic targets for acute hypoxic stress.
Main Methods:
- Utilized next-generation sequencing for gene expression profiling in human AC16 cardiomyocytes.
- Employed bioinformatics analysis, including the miRmap database, to predict miRNA-mRNA interactions.
- Integrated data from the Gene Expression Omnibus database for cross-validation.
Main Results:
- Identified 24 genes with potential miRNA-mRNA interactions (15 upregulated, 9 downregulated).
- Confirmed upregulation of tensin 1, B-cell lymphoma 2-interacting protein 3 like, and stanniocalcin 1 under hypoxia.
- Confirmed downregulation of transferrin receptor and methyltransferase like 7A under hypoxia.
- Identified two key miRNA-mRNA interactions: hsa-miR-129-5p/CDC42EP3 and hsa-miR-330-3p/HELZ.
Conclusions:
- The study provides insights into gene expression changes and miRNA-mRNA interactions in hypoxic cardiomyocytes.
- Findings suggest potential novel diagnostic and therapeutic strategies for conditions like acute myocardial infarction.
- Introduced a novel approach for investigating acute hypoxic pathophysiology in cardiomyocytes.
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.
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