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

• Published in: Molecular therapy. Nucleic acids Vol. 18; pp. 1 - 15
• Main Authors: Yang, Jie, Gong, Yafan, Cai, Jingzeng, Liu, Qi, Zhang, Ziwei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-12-2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Apoptosis; calcium overload; Calcium-binding protein; Cardiomyocytes; chicken heart; Disease; Embryos; Gene expression; Genomics; Heart; Homeostasis; Kinases; lnc3-215-miR1594-TNNT2 axis; MicroRNAs; miRNA; mRNA; Muscle contraction; Nutrient deficiency; Physiology; Proteins; Selenium; selenium deficiency; Troponin; Troponin T; Switzerland; lnc3-215-miR1594-TNNT2 axis; calcium overload; selenium deficiency; chicken heart
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.08.003

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.