Long-noncoding RNA NBR2 via targeting miR-19a-3p regulates pancreatic β cell function and provides novel biomarkers for type 2 diabetes mellitus
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Affiliated Hospital of Weifang Medical University, China
Zhucheng People's Hospital, China
Xinying Song   

Zhucheng People's Hospital, No. 59, South Ring Road, Zhucheng, Weifang, Shando, 262200, Zhucheng, China
Submission date: 2020-12-02
Final revision date: 2021-01-20
Acceptance date: 2021-02-28
Online publication date: 2021-03-20
Type 2 diabetes mellitus (T2DM) is a major kind of diabetes mellitus. This study aimed to analyze the regulatory effect of long noncoding RNA NBR2 on pancreatic  cell function and the related mechanisms, and to analyze the clinical significance of abnormal NBR2 expression in patients with T2DM.

Material and methods:
The expression levels of NBR2 and microRNA-19a-3p (miR-19a-3p) were measured using quantitative Real-Time PCR. The glucose-stimulated insulin secretion was measured using ELISA kit, and cell proliferation was examined using Cell Counting Kit-8 (CCK-8) assay. A dual-luciferase reporter assay was used to confirm the relationship between NBR2 and miR-19a-3p. The diagnostic values of NBR2, miR-19a-3p and NBR2 combined with miR-19a-3p were assessed by receiver operating characteristic (ROC) curves.

The insulin secretion and proliferation of INS-1 cells were inhibited by NBR2 overexpression, and were promoted by NBR2 knockdown. MiR-19a-3p, which was inhibited by NBR2 overexpression, directly mediated the regulatory effects of NBR2 on INS-1 cell function. Increased serum NBR2 level and decreased serum miR-19a-3p level were found in T2DM patients, and a negative correlation was found between NBR2 and miR-19a-3p. The fasting plasma glucose of T2DM patients was positively correlated with serum NBR2 and negatively correlated with serum miR-19a-3p. Both serum NBR2 and miR-19a-3p had certain diagnostic accuracy, whereas, the combined detection of the serum NBR2 and miR-19a-3p showed more considerable diagnostic accuracy.

Our findings indicated that NBR2/miR-19a-3p axis regulates pancreatic β cell function, while may be novel biomarkers for the diagnosis of T2DM.