Mol Ther Nucleic Acids . 2019 Dec 6;18:1-15. doi: 10.1016/j.omtn.2019.08.003.

lnc-3215 Suppression Leads to Calcium Overload in Selenium Deficiency-Induced Chicken Heart Lesion via the lnc-3215-miR-1594-TNN2 Pathway

Jie Yang  1 Yafan Gong  1 Jingzeng Cai  1 Qi Liu  1 Ziwei Zhang  2

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. Electronic address: zhangziwei@neau.edu.cn.

Abstract

Selenium deficiency has been proven to induce calcium disorders in the chicken heart. However, detailed regulatory mechanisms, e.g., the long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory axis, have not yet been described. Here, we point out lnc-2315, miR-1594, and Troponin T (TNNT2) based on the results of lncRNA and miRNA comparative genomics group analysis of Se-deficient chicken hearts compared with control hearts. We employed lnc-3215 and TNNT2 knockdown, miR-1594 knockdown, and overexpression models in the chicken embryos in vivo, and lnc-3215, miR-1594, and TNNT2 knockdown and overexpression models in cardiomyocytes in vitro. The dual-luciferase reporter assay and quantitative real-time PCR were used to confirm the relationships between miR-1594 and TNNT2, lnc-3215, and miR-1594 in cardiomyocytes. Our results revealed that TNNT2 suppression induced cardiac calcium overload in vivo and in vitro. miR-1594 activates cardiac calcium overload by targeting TNNT2. Moreover, we found that lnc-3215 regulates miR-1594, and thus influences the TNNT2 expression in vivo and in vitro; these conclusions were verified by gene knockdown in chicken embryos. Our present study revealed a novel regulatory model of a calcium program, which comprises lnc-3215, miR-1594, and TNNT2 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se-deficient cardiomyocytes injury.

Keywords: calcium overload; chicken heart; lnc3-215-miR1594-TNNT2 axis; selenium deficiency.

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