长链非编码RNA PTGS2通过miR-146a-5p/RBP4轴调节胰岛β细胞功能及其在2型糖尿病中的诊断价值。
LncRNA PTGS2 regulates islet β-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus.
作者信息
Chen Qian, He Yun, Wang Xufeng, Zhu Yong, Huang Yongyao, Cao Jun, Yan Ruicheng
机构信息
Department of Gastrointestinal Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430061, Hubei Province, China.
Hubei Province Academy of Traditional Chinese Medicine Wuhan 430074, Hubei Province, China.
出版信息
Am J Transl Res. 2021 Oct 15;13(10):11316-11328. eCollection 2021.
OBJECTIVE
To investigate the effect of long non-coding RNA (LncRNA) PTGS2 on islet β-cell function via the miR-146a-5p/Retinol binding protein 4 (RBP4) axis and its diagnostic value in type 2 diabetes mellitus (T2DM).
METHODS
The Gene Expression Omnibus (GEO) was analyzed and LncRNA PTGS2 was identified as a potential regulator of T2DM. Mouse pancreatic β cell INS-1 cells were cultured with high glucose, and the relative expression of LncRNA PTGS2 in the serum of T2DM patients and INS-1 cells was detected by Fluorescence Quantitative PCR (qRT-PCR) and its diagnostic value for T2DM was analyzed. The PTGS2/miR-146a-5p/RBP4 axis in INS-1 cells was intervened to observe the changes in cell function. The proliferation of INS-1 cells was detected by CCK8, and the level of insulin secretion was detected by enzyme linked immunosorbent assay (ELISA). The regulatory relationship among LncRNA PTGS2, miR-146a-5p and RBP4 was determined by dual-luciferase reporter assay.
RESULTS
The expression of LncRNA PTGS2 in the serum of T2DM patients increased, and the expression of LncRNA PTGS2 was positively correlated with the fasting blood glucose level of patients (R=0.306, P<0.05). Knockdown of LncRNA PTGS2 could promote the proliferation and insulin secretion of INS-1 cells, while overexpression of LncRNA PTGS2 showed the opposite results (all P<0.05). Knockdown of LncRNA PTGS2 could up-regulate the expression of miR-146a-5p. Overexpression of LncRNA PTGS2 inhibited the proliferation and insulin secretion of INS-1 cells, while miR-146a-5p could partially reverse this effect. RBP4 has been identified as a downstream target gene of miR-146a-5p. Overexpression of miR-146a-5p could inhibit the expression of RBP4, which was positively correlated withLncRNA PTGS2 regulation. The effect of RBP4 on INS-1 cells was the same as that of LncRNA PTGS2.
CONCLUSION
LncRNA PTGS2 can damage islet β-cell function by regulation of miR-146a-5p and up-regulation of RBP4. LncRNA PTGS2 has potential value in the diagnosis of T2DM.
目的
探讨长链非编码RNA（LncRNA）PTGS2通过miR-146a-5p/视黄醇结合蛋白4（RBP4）轴对胰岛β细胞功能的影响及其在2型糖尿病（T2DM）中的诊断价值。
方法
分析基因表达综合数据库（GEO），确定LncRNA PTGS2为T2DM的潜在调节因子。用高糖培养小鼠胰腺β细胞INS-1细胞，采用荧光定量PCR（qRT-PCR）检测T2DM患者血清和INS-1细胞中LncRNA PTGS2的相对表达，并分析其对T2DM的诊断价值。干预INS-1细胞中的PTGS2/miR-146a-5p/RBP4轴，观察细胞功能变化。采用CCK8检测INS-1细胞的增殖情况，采用酶联免疫吸附测定（ELISA）检测胰岛素分泌水平。通过双荧光素酶报告基因检测确定LncRNA PTGS2、miR-146a-5p和RBP4之间的调控关系。
结果
T2DM患者血清中LncRNA PTGS2表达升高，且LncRNA PTGS2表达与患者空腹血糖水平呈正相关（R=0.306，P<0.05）。敲低LncRNA PTGS2可促进INS-1细胞增殖和胰岛素分泌，而LncRNA PTGS2过表达则结果相反（均P<0.05）。敲低LncRNA PTGS2可上调miR-146a-5p的表达。LncRNA PTGS2过表达抑制INS-1细胞增殖和胰岛素分泌，而miR-146a-5p可部分逆转这种作用。RBP4已被确定为miR-146a-5p的下游靶基因。miR-146a-5p过表达可抑制RBP4的表达，其与LncRNA PTGS2调控呈正相关。RBP4对INS-1细胞的作用与LncRNA PTGS2相同。
结论
LncRNA PTGS2可通过调控miR-146a-5p和上调RBP4损害胰岛β细胞功能。LncRNA PTGS2在T2DM诊断中具有潜在价值。
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