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非侵入性生物标志物lncRNA GAS5/miR-21 ceRNA调控网络在糖尿病及糖尿病肾病早期诊断中的相关性

The relevance of the non-invasive biomarkers lncRNA GAS5/miR-21 ceRNA regulatory network in the early identification of diabetes and diabetic nephropathy.

作者信息

Sun He, Chen Tong, Li Xin, Zhu Yonghong, Zhang Shuang, He Ping, Peng Yali, Fan Qiuling

机构信息

Department of Nephrology, The First Hospital of China Medical University, Shenyang, China.

Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Diabetol Metab Syndr. 2023 Oct 11;15(1):197. doi: 10.1186/s13098-023-01179-7.

Abstract

BACKGROUND

To investigate the diagnostic value of serum lncRNA growth arrest-specific transcript 5 (lncRNA GAS5) and microRNA-21 (miR-21) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and elucidate their roles in the pathogenesis.

METHODS

A microarray technology was used asses lncRNA GAS5 and miR-21 expression profiles in non-anticoagulant blood from 44 patients including T2DM without DN group (DM), T2DM with DN group (DN), and healthy controls group (N), followed by real-time PCR validation. Logistic regression and receiver operating characteristic (ROC) curves were applied to evaluate the clinical indicators among normal, T2DM, and DN patients.

RESULTS

The serum lncRNA GAS5 expression in T2DM and DN patients was significantly down-regulated compared with the N group, while the expression of miR-21 was significantly up-regulated (all P < 0.05). Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) were negatively correlated with serum lncRNA GAS5, and FBG was independently correlated with serum lncRNA GAS5. Urinary microalbumin, total cholesterol (TC), creatinine (Cr), urea, and systolic blood pressure (SBP) were significantly positively correlated with serum miR-21. Glomerular filtration rate (GFR) and albuminuria (ALB) were negatively correlated with serum miR-21, and ALB was independently correlated with serum miR-21. Serum lncRNA GAS5, miR-21 and lncRNA GAS5/miR-21 showed good diagnostic efficiency as the "diagnostic signature" of T2DM and DN.

CONCLUSION

The lncRNA GAS5/miR-21 diagnostic signature may be a more effective non-invasive biomarker for detecting T2DM. In addition, miR-21 alone may be a more accurate serum biomarker for the early screening of DN patients.

摘要

背景

探讨血清长链非编码RNA生长停滞特异性转录本5(lncRNA GAS5)和微小RNA-21(miR-21)在2型糖尿病(T2DM)及糖尿病肾病(DN)患者中的诊断价值,并阐明它们在发病机制中的作用。

方法

采用基因芯片技术检测44例患者非抗凝血液中lncRNA GAS5和miR-21的表达谱,包括无DN的T2DM组(DM)、伴DN的T2DM组(DN)和健康对照组(N),随后进行实时荧光定量PCR验证。应用逻辑回归和受试者工作特征(ROC)曲线评估正常、T2DM和DN患者的临床指标。

结果

与N组相比,T2DM和DN患者血清lncRNA GAS5表达显著下调,而miR-21表达显著上调(均P<0.05)。空腹血糖(FBG)和糖化血红蛋白(HbA1c)与血清lncRNA GAS5呈负相关,且FBG与血清lncRNA GAS5独立相关。尿微量白蛋白、总胆固醇(TC)、肌酐(Cr)、尿素和收缩压(SBP)与血清miR-21显著正相关。肾小球滤过率(GFR)和蛋白尿(ALB)与血清miR-21呈负相关,且ALB与血清miR-21独立相关。血清lncRNA GAS5、miR-21及lncRNA GAS5/miR-21作为T2DM和DN的“诊断标志物”显示出良好的诊断效能。

结论

lncRNA GAS5/miR-21诊断标志物可能是检测T2DM更有效的非侵入性生物标志物。此外,单独的miR-21可能是早期筛查DN患者更准确的血清生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e39c/10566063/e408e49037ee/13098_2023_1179_Fig1_HTML.jpg

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