Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic beta-cell Function by Sponging miR-766-3p to Upregulate NR3C2
Elevated Circulating LINC-P21 Serves as a Diagnostic Biomarker of Type 2 Diabetes Mellitus and Regulates Pancreatic beta-cell Function by Sponging miR-766-3p to Upregulate NR3C2
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DOI：
10.1055/a-1247-4978
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发表时间：
2020-10-02
影响因子：
1.8
通讯作者：
Feng, Xueqiang
中科院分区：
文献类型：
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作者：
Cao, Zhibin;Yao, Fuwang;Feng, Xueqiang
目的评价长非编码RNA(LncRNA)LINC-P21在2型糖尿病(T2 DM)中的临床价值和生物学功能，探讨其可能的作用机制。通过功能得失实验探讨LINC-P21的功能作用。用细胞计数试剂盒-8(CCK-8)分析INS-1细胞的增殖情况，用ELISA法测定葡萄糖刺激的胰岛素分泌。结果T2 DM患者血清LINC-P21表达水平升高，与空腹血糖水平及疾病诊断相关。LINCP21基因敲除可促进葡萄糖刺激的胰岛素分泌和INS-1细胞的增殖，而过表达LINC-P21则相反。MIR-766-3p可被LINC-P21直接抑制INS-1细胞，并逆转LINC-P21对3-细胞功能的影响。此外，NR3C2被确定为miR-766-3p的靶点，它可以被LINCP21正向调节，并且与LINC-P21对INS-1细胞增殖和胰岛素分泌的作用相同。结论血清LINC-P21升高和miR-766-3p降低可作为T2 DM的候选诊断生物标志物。LINC-P21通过靶向miR-766-3p上调NR3C2，在胰岛素分泌和胰岛β细胞增殖中发挥潜在的调节作用。
Objective The purpose of this study was to evaluate the clinical value and biological function of long non-coding RNA (lncRNA) LINC-P21 in type 2 diabetes mellitus (T2DM), and explore the underlying mechanisms.Methods The expression of LINC-P21 was estimated using quantitative real-time PCR. The functional role of LINC-P21 was explored by gain- and loss-of-function experiments. INS-1 cell proliferation was analyzed using a cell counting kit-8 (CCK-8) assay, and the glucose-stimulated insulin secretion was measured using an ELISA kit. The miRNAs that might be sponged by LINC-P21 were analyzed, and the subsequent target genes were predicted and assessed in INS-1 cells.Results Serum expression of LINC-P21 was elevated in T2DM patients, which was correlated with fasting blood glucose levels and disease diagnosis. The glucose-stimulated insulin secretion and the proliferation of INS-1 cells were enhanced by LINCP21 knockdown, but the overexpression of LINC-P21 led to opposite effects. miR-766-3p could be directly inhibited by LINC-P21 in INS-1 cells and reverse the effects of LINC-P21 on (3-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINCP21 and had same effects with LINC-P21 on INS-1 cell proliferation and insulin secretion.Conclusion All the data demonstrated that serum elevated LINC-P21 and decreased miR-766-3p serve as candidate diagnostic biomarkers in T2DM patients. LINC-P21 acts as a potential regulator in insulin secretion and proliferation of pancreatic beta-cells through targeting miR-766-3p to upregulate NR3C2.