Screening of circular RNAs and validation of circANKRD36 associated with inflammation in patients with type 2 diabetes mellitus.
Screening of circular RNAs and validation of circANKRD36 associated with inflammation in patients with type 2 diabetes mellitus.
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与2型糖尿病患者炎症相关的环状RNA的筛选和circANKRD36的验证
DOI：
10.3892/ijmm.2018.3783
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发表时间：
2018-10
影响因子：
5.4
通讯作者：
Zou L
中科院分区：
文献类型：
--
作者：
Fang Y;Wang X;Li W;Han J;Jin J;Su F;Zhang J;Huang W;Xiao F;Pan Q;Zou L
环状RNA（circRNA）是一类丰富的内源性非编码RNA，并且与许多疾病相关，包括癌症、心血管疾病和2型糖尿病（T2 DM）。然而，T2 DM患者中circRNA与炎症或炎性细胞因子之间的关联仍有待充分阐明。本研究的目的是探讨2型糖尿病患者外周血白细胞中circRNA的表达谱及其与炎性细胞因子的关系。采集T2 DM患者（n=43）和健康个体（n=45）的外周血进行RNA测序和后续验证。采用逆转录-聚合酶链反应（RT-PCR）和逆转录-定量聚合酶链反应（RT-qPCR）分析circRNA的表达水平。采用酶联免疫吸附法（ELISA）检测各组大鼠血清中白细胞介素（IL）-1、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α的表达。此外，使用RT-qPCR分析测量锚蛋白重复结构域36（ANKRD 36）（位于2q11.2的与GAPDH基因相互作用的蛋白质）的mRNA表达水平。使用RegRNA和mirPath软件预测circRNA/microRNA（miRNA）相互作用。总共发现220个circRNA在T2 DM患者和健康个体之间差异表达，其中107个上调，113个下调。在9种选择的circRNA中，与对照受试者相比，T2 DM患者的circANKRD 36显著上调（P=0.02）。circANKRD 36的表达水平与血糖和糖化血红蛋白呈正相关（r分别为0.3250，P=0.0047和r=0.3171，P=0.0056）。T2 DM组IL-6的表达水平与对照组相比差异有统计学意义（P=0.028），且与circANKRD 36呈正相关。2型糖尿病患者与健康对照者circANKRD 36宿主基因表达差异有统计学意义（P=0.04）。综上所述，circANKRD 36可能通过与miRNA（包括hsa-miR-3614- 3 p、hsa-miR-498和hsa-miR-501- 5 p）相互作用参与T2 DM和炎症相关途径。T2 DM患者外周血白细胞中circANKRD 36表达上调，与慢性炎症相关。因此，circANKRD 36可作为筛选T2 DM患者慢性炎症的潜在生物标志物。
Circular RNAs (circRNAs) are an abundant class of endogenous non-coding RNAs and are associated with numerous diseases, including cancer, cardiovascular diseases, and type 2 diabetes mellitus (T2DM). However, the association between circRNAs and inflammation or inflammatory cytokines in patients with T2DM remains to be fully elucidated. The purpose of the present study was to investigate the expression profiles of circRNAs in peripheral leucocytes of patients with T2DM and their association with inflammatory cytokines. Peripheral blood from patients with T2DM (n=43) and healthy individuals (n=45) were collected for RNA sequencing and later verification. Reverse transcription-polymerase chain reaction (RT-PCR) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were used to detect the expression levels of circRNAs. The expression of inflammatory factors, including interleukin (IL)-1, (IL)-6, and tumor necrosis factor (TNF)-α were measured via enzyme-linked immunosorbent assay. Furthermore, the mRNA expression level of ankyrin repeat domain 36 (ANKRD36), a protein located at 2q11.2 that interacts with the GAPDH gene, was measured using RT-qPCR analysis. The circRNA/microRNA (miRNA) interaction was predicted using RegRNA and mirPath software. In total, 220 circRNAs were found to be differentially expressed between patients with T2DM and healthy individuals, of which 107 were upregulated and 113 were downregulated. Among the nine selected circRNAs, circANKRD36 was significantly upregulated in patients with T2DM compared with control subjects (P=0.02). The expression level of circANKRD36 was positively correlated with glucose and glycosylated hemoglobin (r=0.3250, P=0.0047 and r=0.3171, P=0.0056, respectively). The expression level of IL-6 was significantly different between the T2DM group and control group (P=0.028) and was positively correlated with circANKRD36. The difference of circANKRD36 host gene expression between patients with T2DM and healthy controls was significant (P=0.04). Taken together, circANKRD36 may be involved in T2DM and inflammation-associated pathways via interaction with miRNAs, including hsa-miR-3614-3p, hsa-miR-498, and hsa-miR-501-5p. The expression of circANKRD36 was up regulated in peripheral blood leucocytes and was correlated with chronic inflammation in T2DM. Therefore, circANKRD36 can be used as a potential biomarker for screening chronic inflammation in patients with T2DM.
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作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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