LINC-p21 Regulates Pancreatic β-Cell Function in Type 2 Diabetes Mellitus.

IF 2.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-06-12 DOI:10.1007/s10528-024-10850-1

Zengkun Qian, Fan Cui, Zheng Mao, Zhen Li, Xiayu Yi, Jingjing Zhou, Jinjin Cao, Xiaoqin Li

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Abstract

This study aimed to investigate the underlying mechanism and assess the biological role of long intergenic non-coding RNA (LINCRNA)-p21 in type 2 diabetes mellitus (T2DM). LINC-p21 and miR-335-3p expression levels were evaluated in blood from T2DM patients, healthy individuals, and mouse islet β-cell line MIN6 cells grown in a high glucose environment. Apoptosis-related proteins, iNOS, and IGF-1 were detected in vitro and in vivo. Bioinformatics was used to predict that miR-335-3p had complementary binding sites to IGF-1, and a dual-luciferase reporter confirmed the targeting link between LINC-p21 and miR-335-3p. LINC-p21 was highly expressed in the T2DM serum and cells, and LINC-p21 was significantly associated with T2DM prognosis. In vitro and in vivo dysfunction of β-cells was reduced by LINC-p21 knockdown. MiR-335-3p and IGF-1 may be potential targets of LINC-p21 and miR-335-3p, respectively, after the prediction of the target of LINC-p21 was verified by dual-luciferase assay. Anti-miR-335-3p made LINC-p21 knockdown function again; however, interference of IGF-1 mRNA restored the function of LINC-p21. The miR-335-3p/IGF-1 axis may have a role in the functional protection of pancreatic β-cells by LINC-p21 silencing, boosting insulin production, and slowing the course of diabetes.

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LINC-p21调控2型糖尿病患者的胰腺β细胞功能

本研究旨在探究长基因间非编码 RNA（LINCRNA）-p21 在 2 型糖尿病（T2DM）中的潜在机制并评估其生物学作用。研究人员评估了 T2DM 患者、健康人和在高糖环境下生长的小鼠胰岛β细胞系 MIN6 细胞血液中 LINC-p21 和 miR-335-3p 的表达水平。在体外和体内检测了凋亡相关蛋白、iNOS 和 IGF-1。生物信息学预测 miR-335-3p 与 IGF-1 有互补结合位点，双荧光素酶报告证实了 LINC-p21 与 miR-335-3p 之间的靶向联系。LINC-p21在T2DM血清和细胞中高表达，LINC-p21与T2DM的预后显著相关。LINC-p21被敲除后，β细胞的体外和体内功能障碍均有所减轻。通过双荧光素酶检测验证了LINC-p21的靶点预测，MiR-335-3p和IGF-1可能分别是LINC-p21和miR-335-3p的潜在靶点。抗miR-335-3p使LINC-p21的功能再次被敲除，而干扰IGF-1 mRNA则恢复了LINC-p21的功能。miR-335-3p/IGF-1轴可能在通过LINC-p21沉默保护胰岛β细胞功能、促进胰岛素分泌和延缓糖尿病进程中发挥作用。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.