长链非编码-PRL-12:1调控整合素亚单位β3和整合素亚单位α2b促进2型糖尿病合并代谢相关脂肪性肝病的研究  

Long non-coding-PRL-12:1 regulates Integrin-B3 and integrin x2b and promotes type 2 diabetes mellitus with metabolic associated fatty liver disease

作　　者：李敏[1] 汤新乐 张丽[3] 杨艳艳 徐卉 LI Min;TANG Xinde;ZHANG Li(Department of Endocrinology,The Sith Affiliated Hospital of Xinjiang Medical University,Urunqi 830092,China)

机构地区：[1]新疆医科大学第六附属医院内分泌科,乌鲁木齐830092 [2]新疆医科大学第六附属医院检验科,乌鲁木齐830092 [3]新疆医科大学第五附属医院内分泌科

出　　处：《中国糖尿病杂志》2024年第7期488-494,共7页Chinese Journal of Diabetes

基　　金：新疆维吾尔自治区自然科学基金(2020D01A128);新疆医科大学第六附属医院科研专项基金-在读博士专项基金(LFYKYZX2023-16)。

摘　　要：目的 探讨长链非编码RNA(lnc RNA)调控整合素亚单位β3(ITGB3)和整合素亚单位α2b(ITGA2B)促进T2DM合并代谢相关脂肪性肝病(MAFLD)的分子机制。方法 选取2020年12月至2021年12月于新疆医科大学第六附属医院内分泌科住院治疗的T2DM患者(T2DM组)和T2DM合并MAFLD患者(MAFLD组),每组各15例,另选取同期门诊体检健康者15名为正常对照(NC)组。收集各组外周血单个核细胞(PBMC)样本,各组随机选取3例样本应用高通量测序鉴定差异表达基因(DEm RNAs和DElnc RNAs),进行生物信息学分析和RT-qPCR检测。结果 与NC组比较,T2DM、MAFLD组中有594个共同的DEm RNAs和158个共同的DElnc RNAs,并聚类为28个共表达模块,其中plum2模块与MAFLD组相关性最高。进一步在plum2模块中构建lnc RNA-m RNA调控网络,受到lnc-PRL-12:1调控的ITGB3和ITGA2B参与最多的信号通路,包括凝血,ECM-受体相互作用,磷脂酰肌醇3-激酶/蛋白激酶B信号通路等。MAFLD组lnc-PRL-12:1、ITGB3和ITGA2B m RNA表达高于NC、T2DM组(P<0.05)。结论 lnc-PRL-12:1可能通过调控ITGB3和ITGA2B表达参与T2DM合并MAFLD的病理机制。Objective To investigatethe molecular mechanism that long non-coding RNA(lncRNA)regulates integrin subunitβ3(ITGB3)and integrin subunitα2b(ITGA2B)to promote type 2 diabetes mellitus(T2DM)complicated with metabolic-related fatty liver disease(MAFLD).Methods A total of 30 hospitalized patients with T2DM were enrolled in this study from the Endocrinology Department in the Sixth Affiliated Hospital of Xinjiang Medical University during December 2020 to December 2021.All the patients were divided into two groups,T2DM group(n=15)and T2DM with MAFLD group(n=15).In addition,healthy controls were recruited as control group(NC,n=15).Peripheral blood mononuclear cell samples were collected from the participants.Three samples were randomly selected from each group,and then high throughput sequencing was done to identify differentially expressed genes(DEmRNAs and DElncRNAs).Subsequently,bioinformatics analysis,and RT-qPCR detection were performed.Results Compared with NC group,there were 594 common DEmRNAs and 158 common DElncRNAs in T2DM group and MAFLD group,and they were further clustered into 28 co-expression modules,of which the plum2 module had the highest correlation with T2DM with MAFLD.Further,the IncRNA-mRNA regulatory network was constructed in the plum2 module.ITGB3 and ITGA2B,which were regulated by lnc-PRL-12:1,were involved in most of the signaling pathways,including coagulation,extracellular matrix-receptor interaction,phosphatidylinositol 3/kinase-protein kinase B(PI3K-Akt)signaling pathway,etc.Lnc-PRL-12:1,ITGB3,and ITGA2B were significantly expressedhigher in MAFLD group than in T2DM and NC group.Conclusions The Inc-PRL-12:lmay regulate expression of ITGB3 and ITGA2B and participate in the pathological mechanism of T2DM with MAFLD.

关 键 词：糖尿病 2型 代谢相关脂肪性肝病 长链非编码RNA 

分 类 号：R587.1[医药卫生—内分泌] R575.5[医药卫生—内科学]