Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes.
Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes.
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DOI：
10.1186/s40246-018-0173-3
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发表时间：
2018-08-23
期刊：
影响因子：
4.5
通讯作者：
Balasubramanyam M
中科院分区：
文献类型：
--
作者：
Sathishkumar C;Prabu P;Mohan V;Balasubramanyam M
表观遗传学的研究有望在基因组水平上提供有关环境因素如何导致2型糖尿病（T2DM）的宝贵信息。随着全基因组重测序工作的进展，现在已知75 - 90%的人类基因组被转录以产生一系列长的非编码RNA（lncRNA）。虽然lncRNA作为几种疾病状态的发生和进展中的潜在和稳健的生物标志物而受到广泛关注，但其临床相关性和调控机制在包括糖尿病在内的代谢紊乱领域仍有待探索。尽管事实上亚洲印度人是高度胰岛素抵抗的，并且更容易发展为T2DM和相关的血管并发症，但实际上缺乏关于lncRNA在临床糖尿病环境中的作用的数据。因此，我们试图评估与正常葡萄糖耐量个体（NGT; n = 32）相比，2型糖尿病（T2DM; n = 30）患者外周血单核细胞（PBMC）中的一组lncRNA和衰老-炎症特征。与对照受试者相比，来自2型糖尿病患者的PBMC中lncRNA的表达水平显示HOTAIR、MEG3、LET、MALAT1、MIAT、CDKN 2BAS 1/ANRIL、XIST、PANDA、GAS 5、Linc-p21、ENST 00000550337.1、PLUTO和NBR 2的水平显著（p <0.05）增加。相比之下，T2DM患者中THRIL和SALRNA1的lncRNA表达模式与对照受试者相比显著降低（p <0.05）。在转录水平上，与对照组相比，2型糖尿病患者的衰老标志物（p53、p21、p16和β-半乳糖苷酶）、促炎标志物（TNF-α、IL 6、MCP 1和IL 1-β）以及组蛋白脱乙酰酶-3（HDAC 3）的表观遗传特征显著升高（p <0.05）。有趣的是，与对照组相比，2型糖尿病患者的Sirt1 mRNA表达和端粒长度显著降低（p <0.05）。大多数改变的lncRNA与血糖控制不良、胰岛素抵抗、衰老转录标志物、炎症和HDAC3正相关，与端粒长度负相关。Logistic回归分析显示lncRNA特征改变与T2DM显著相关，但在调整胰岛素抵抗（HOMA-IR）和衰老标志物后，这种相关性消失。我们的研究为改变的lncRNA与血糖控制不良、胰岛素抵抗、加速细胞衰老和炎症的关联提供了临床相关证据。本文的在线版本（10.1186/s40246 - 018 - 0173 - 3）包含补充材料，可供授权用户使用。
Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75–90% of the human genome was transcribed to generate a series of long non-coding RNAs (lncRNAs). While lncRNAs are gaining widespread attention as potential and robust biomarkers in the genesis as well as progression of several disease states, their clinical relevance and regulatory mechanisms are yet to be explored in the field of metabolic disorders including diabetes. Despite the fact that Asian Indians are highly insulin resistant and more prone to develop T2DM and associated vascular complications, there is virtually lack of data on the role of lncRNAs in the clinical diabetes setting. Therefore, we sought to evaluate a panel of lncRNAs and senescence-inflammation signatures in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes (T2DM; n = 30) compared to individuals with normal glucose tolerance (NGT; n = 32). Compared to control subjects, expression levels of lncRNAs in PBMCs from type 2 diabetes patients showed significantly (p < 0.05) increased levels of HOTAIR, MEG3, LET, MALAT1, MIAT, CDKN2BAS1/ANRIL, XIST, PANDA, GAS5, Linc-p21, ENST00000550337.1, PLUTO, and NBR2. In contrast, lncRNA expression patterns of THRIL and SALRNA1 were significantly (p < 0.05) decreased in patients with T2DM compared to control subjects. At the transcriptional level, senescence markers (p53, p21, p16, and β-galactosidase), proinflammatory markers (TNF-α, IL6, MCP1, and IL1-β), and epigenetic signature of histone deacetylase-3 (HDAC3) were significantly (p < 0.05) elevated in patients with type 2 diabetes compared to control subjects. Interestingly, mRNA expression of Sirt1 and telomere length were significantly (p < 0.05) decreased in patients with type 2 diabetes compared to control subjects. Majority of the altered lncRNAs were positively correlated with poor glycemic control, insulin resistance, transcriptional markers of senescence, inflammation, and HDAC3 and negatively correlated with telomere length. Logistic regression analysis revealed a significant association of altered lncRNA signatures with T2DM, but this association was lost after adjusting for insulin resistance (HOMA-IR) and senescence markers. Our study provides a clinically relevant evidence for the association of altered lncRNAs with poor glycemic control, insulin resistance, accelerated cellular senescence, and inflammation. The online version of this article (10.1186/s40246-018-0173-3) contains supplementary material, which is available to authorized users.
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影响因子：
29
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Akerman I;Tu Z;Beucher A;Rolando DMY;Sauty-Colace C;Benazra M;Nakic N;Yang J;Wang H;Pasquali L;Moran I;Garcia-Hurtado J;Castro N;Gonzalez-Franco R;Stewart AF;Bonner C;Piemonti L;Berney T;Groop L;Kerr-Conte J;Pattou F;Argmann C;Schadt E;Ravassard P;Ferrer J
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The Journal of nutritional biochemistry
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The Indian journal of medical research
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10.1016/j.bbacli.2015.09.001
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