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 LINC-P21 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 β-cell function. Additionally, NR3C2 was determined as a target of miR-766-3p, which could be positively regulated by LINC-P21 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 β-cells through targeting miR-766-3p to upregulate NR3C2.

中文翻译：

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升高的循环 LINC-P21 作为 2 型糖尿病的诊断生物标志物，并通过海绵化 miR-766-3p 上调 NR3C2 调节胰腺 β 细胞功能

目的本研究旨在评价长链非编码RNA（lncRNA）LINC-P21在2型糖尿病（T2DM）中的临床价值和生物学功能，并探讨其作用机制。方法使用实时定量PCR估计LINC-P21的表达。LINC-P21 的功能作用通过增益和功能丧失实验进行了探索。使用细胞计数试剂盒 8 (CCK-8) 分析分析 INS-1 细胞增殖，并使用 ELISA 试剂盒测量葡萄糖刺激的胰岛素分泌。分析了 LINC-P21 可能吸收的 miRNA，并在 INS-1 细胞中预测和评估了随后的靶基因。结果 T2DM患者血清LINC-P21表达升高，与空腹血糖水平和疾病诊断相关。LINC-P21 敲低增强了葡萄糖刺激的胰岛素分泌和 INS-1 细胞的增殖，但 LINC-P21 的过表达导致相反的效果。miR-766-3p 可直接被 INS-1 细胞中的 LINC-P21 抑制，并逆转 LINC-P21 对 β 细胞功能的影响。此外，NR3C2 被确定为 miR-766-3p 的靶标，可被 LINC-P21 正向调节，并且与 LINC-P21 对 INS-1 细胞增殖和胰岛素分泌具有相同的作用。结论 所有数据表明，血清 LINC-P21 升高和 miR-766-3p 降低可作为 T2DM 患者的候选诊断生物标志物。LINC-P21 通过靶向 miR-766-3p 上调 NR3C2 作为胰岛素分泌和胰腺 β 细胞增殖的潜在调节剂。