Changes in liver microRNA expression and their possible regulatory role in energy metabolism-related genes in hibernating black bears
Changes in liver microRNA expression and their possible regulatory role in energy metabolism-related genes in hibernating black bears
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DOI：
10.1007/s00360-020-01337-7
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Kazuhei Nishida;Michito Shimozuru;Y. Okamatsu-Ogura;Mitsunori Miyazaki;Tsukasa Soma;M. Sashika;T. Tsubota
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文献类型：
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作者：
Kazuhei Nishida;Michito Shimozuru;Y. Okamatsu-Ogura;Mitsunori Miyazaki;Tsukasa Soma;M. Sashika;T. Tsubota
冬眠的熊可以在不进食的情况下存活长达6个月，同时保持代谢平衡。我们先前报道了冬眠的日本黑熊肝脏中能量代谢相关基因的表达变化。本研究探讨了microRNA在冬眠期间肝脏基因表达调控中的作用。定量分析显示，在冬眠期间，4种microRNA（miR-221- 3 p、miR-222- 3 p、miR-455- 3 p和miR-195 a-5 p）的表达显著增加，2种microRNA（miR-122- 5 p和miR-7a-1- 5 p）的表达显著减少。对3种上调的microRNA（miR-221- 3 p、miR-222- 3 p和miR-455- 3 p）进行RNA测序和计算机靶向预测，发现13种靶mRNA在冬眠期间表达显著降低。将microRNA模拟物转染到细胞中显示，miR-222和miR-455分别降低溶质载体家族16成员4（SLC 16 A4）和脂肪酸合成酶（FATCH）mRNA表达。我们的研究结果表明，在冬眠期间增加的肝脏miRNA（miR-222- 3 p和miR-455- 3 p）水平负调控靶基因的表达预测参与能源的运输和从头脂肪酸的合成，这与这些miRNA在冬眠黑熊的能量代谢中的调节作用是一致的。
Hibernating bears survive up to 6 months without feeding while yet maintaining metabolic homeostasis. We previously reported expression changes in energy metabolism-related genes in the liver of hibernating Japanese black bears. The present study examined the role of microRNAs in the regulation of hepatic gene expression during hibernation. The quantitative analyses revealed significant increases in the expression of 4 microRNAs (miR-221-3p, miR-222-3p, miR-455-3p, and miR-195a-5p) and decreases of 2 microRNAs (miR-122-5p and miR-7a-1-5p) during hibernation. RNA sequencing and in silico target prediction regarding 3 upregulated microRNAs (miR-221-3p, miR-222-3p and miR-455-3p) found 13 target mRNAs with significantly decreased expression during hibernation. The transfection of microRNA mimics into cells showed that miR-222 and miR-455 reduced solute carrier family 16 member 4 (SLC16A4) and fatty acid synthase(FASN) mRNA expression, respectively. Our results suggest that the increased levels of hepatic miRNA during hibernation (miR-222-3p and miR-455-3p) negatively regulate the expression of targeted genes predicted to be involved in the transport of energy source and de novo fatty acid synthesis, is consistent with a regulatory role of these miRNAs in energy metabolism in hibernating black bears.