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RNA-Seq of wild type and miR-574 knockout mouse hearts at baseline

ABSTRACT: Purpose: The target mRNAs of miR-574 in mouse heart are unknown. The goal of this study is to use next generation sequencing (NGS) RNA-seq followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods to identify the downstream target genes that are directly regulated by miR-574 in murine hearts at the mRNA level. Results: Using a well established data analysis workflow from the Genomic Research Center from University of Rochester Medical Center, we analyzed RNA-seq data. We have identified novel genes that are regulated by miR-574 via miRNA-induced silencing complex (miRISC). We defined differentially regulated genes (either upregulated or downregulated) with statistical significance in total RNA expression change (p value <0.05 for differential expressed genes). We identified 34 upregulated genes involved in the small molecule metabolism and the mitochondrial function, and 49 downregulated genes in the electron transport chain (ETC) complex, oxidative phosphorylation, and tricarboxylic acid cycle. Conclusions: Among 34 upregulated genes, eight genes contain the predicted target seed sequence of miR-574-5p and Fam210a (family with sequence similarity 210 member A) is the only upregulated gene that contains the target seed sequence of both the guide strand miR-574-5p and the passenger strand miR-574-3p. We confirmed that FAM210A was the downstream target of both miR-574-5p and miR-574-3p in vivo and in vitro. Based on our results, we conclude that miR-574 downregulates a limited number of mitochondrial function related genes including FAM210A in mouse hearts at baseline.

ORGANISM(S): Mus musculus

PROVIDER: GSE149168 | GEO | 2020/04/23

REPOSITORIES: GEO

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Project description:Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy.

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RNA-Seq of wild type and miR-574 knockout mouse hearts at baseline

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