Correlation analysis of microribonucleic acid-155 and microribonucleic acid-29 with type 2 diabetes mellitus, and the prediction and verification of target genes.

Correlation analysis of microribonucleic acid-155 and microribonucleic acid-29 with type 2 diabetes mellitus, and the prediction and verification of target genes.
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与2型糖尿病的微核酸155和微核酸-29的相关性分析,以及靶基因的预测和验证。

DOI:
10.1111/jdi.13334
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发表时间:
2021-03
影响因子:
3.2
通讯作者:
Zhang J
Zhang J
中科院分区:
医学3区
文献类型:
--
作者:
Zhu J;Wang C;Zhang X;Qiu T;Ma Y;Li X;Pang H;Xiong J;Yang X;Pan C;Xie J;Zhang J

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据报道,microRNA 155和microRNA 29在一些细胞和动物模型中抑制葡萄糖代谢,但目前尚无来自易感人群的证据来检查microRNA 155或microRNA 29与2型糖尿病之间的关系。此外,由microRNA 155和microRNA 29调控的影响葡萄糖和脂质代谢的靶基因仍然未知。人类参与者被分为正常体重组(n = 72),肥胖组(n = 120)和2型糖尿病组(n = 59)。测定血清中microRNA 155和microRNA 29丰度的含量,筛选microRNA 155或microRNA 29靶向的可能与糖脂代谢相关的候选基因。microRNA 155和microRNA 29在HepG 2细胞中的过表达用于验证候选基因的表达,并测量对糖和脂质代谢的影响。microRNA 155和microRNA 29的血清水平显示,与正常体重个体相比,肥胖和2型糖尿病个体的血清水平显著增加。鉴定的microRNA 155的靶基因是MAPK 14、MAP 3 K10、DUSP 14和PRKAR 2B。鉴定的microRNA 29的靶基因是PEX 11 A和FADS 1。microRNA 155或microRNA 29在HepG 2细胞中的过表达被发现下调所鉴定的靶基因的表达,并导致甘油三酯合成和葡萄糖掺入的抑制。2型糖尿病患者中microRNA 155和microRNA 29的表达水平显著高于对照组,且与空腹血糖水平呈正相关,microRNA 155或microRNA 29的过表达可下调HepG 2细胞糖脂代谢靶基因,减少脂质合成和葡萄糖掺入。我们发现,microribonucleic acid-155和microribonucleic acid-29促进2型糖尿病的发展。此外,我们还对其下游靶基因进行了体外筛选和验证。
Microribonucleic acid‐155 (microRNA155) and microRNA29 are reported to inhibit glucose metabolism in some cell and animal models, but no evidence from susceptible populations that examines the relationship between microRNA155 or microRNA29 and type 2 diabetes mellitus currently exists. Furthermore, target genes regulated by microRNA155 and microRNA29 that affect glucose and lipid metabolism remain unknown. Human participants were divided into normal weight (n = 72), obesity (n = 120) and type 2 diabetes (n = 59) groups. The contents of microRNA155 and microRNA29 abundance in serum were measured, and candidate genes potentially related to glucose and lipid metabolism targeted by either microRNA155 or microRNA29 were screened. Overexpression of microRNA155 and microRNA29 in HepG2 cells was used to verify candidate gene expression, and measure the effects on glucose and lipid metabolism. Serum levels of microRNA155 and microRNA29 show a significant increase in individuals with obesity and type 2 diabetes compared with normal weight individuals. Identified target genes for microRNA155 were MAPK14, MAP3K10, DUSP14 and PRKAR2B. Identified target genes for microRNA29 were PEX11A and FADS1. Overexpression of microRNA155 or microRNA29 in HepG2 cells was found to downregulate the expression of identified target genes, and result in inhibition of triglyceride synthesis and glucose incorporation. MicroRNA155 and microRNA29 were significantly higher in type 2 diabetes patients compared with the control patients, their levels were also positively correlated with fasting plasma glucose levels, and over‐expression of microRNA155 or microRNA29 were found to downregulate glucose and lipid metabolism target genes, and reduce lipid synthesis and glucose incorporation in HepG2 cells. We found that microribonucleic acid‐155 and microribonucleic acid‐29 promote the development of type 2 diabetes mellitus. In addition, we screened and validated its downstream target genes in vitro.
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