[1]李晓华,聂文强,莫婷婷,等.lncRNA KCNQ1OT1通过miR-124-3p调控SOCS5对大鼠糖尿病性骨质疏松症的作用及机制实验研究[J].陕西医学杂志,2025,54(9):1170-1176.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.003]
　LI Xiaohua,NIE Wenqiang,MO Tingting,et al.Effect and mechanism of lncRNA KCNQ1OT1 on diabetic osteoporosis in rats by regulating SOCS5 through miR-124-3p[J].,2025,54(9):1170-1176.[doi:DOI:10.3969/j.issn.1000-7377.2025.09.003]
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lncRNA KCNQ1OT1通过miR-124-3p调控SOCS5对大鼠糖尿病性骨质疏松症的作用及机制实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年9期
页码:
1170-1176
栏目:
基础研究
出版日期:
2025-09-05

文章信息/Info

Title:
Effect and mechanism of lncRNA KCNQ1OT1 on diabetic osteoporosis in rats by regulating SOCS5 through miR-124-3p
作者:
李晓华1; 聂文强2; 莫婷婷1; 杨光宇3
（1.广东药科大学附属第一医院全科医学科，广东 广州 510030；2.广东药科大学附属第一医院中医科，广东 广州 510030；3.广州市疾病预防控制中心毒理学检验部，广东 广州 510440）
Author(s):
LI Xiaohua1; NIE Wenqiang2; MO Tingting1; YANG Guangyu3
(1.Department of General Medicine,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510030,China;2.Department of Traditional Chinese Medicine,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510030,China;3.Department of Toxicology and Biochemical Testing,Guangzhou Center for Disease Control and Prevention,Guangzhou 510440,China)
关键词:
糖尿病性骨质疏松症; 长链非编码RNA; 钾电压门控通道亚家族Q成员1重叠转录本1; 微小RNA-124-3p; 细胞因子信号传导抑制因子5; 骨生物力学; 股骨组织
Keywords:
Diabetic osteoporosis; Long non-coding RNA; KCNQ1OT1; miR-124-3p; SOCS5; Bone biomechanics; Femur tissue
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.09.003
文献标志码:
A
摘要:
目的：探讨长链非编码RNA（lncRNA）钾电压门控通道亚家族Q成员1重叠转录本1（KCNQ1OT1）通过微小RNA（miR）-124-3p调控细胞因子信号传导抑制因子5（SOCS5）对大鼠糖尿病性骨质疏松症（DOP）的作用及机制。方法：将72只SD大鼠按照随机数字表法分为六组（每组12只）：假手术（Sham）组、DOP组、si-NC组、si-KCNQ1OT1组、si-KCNQ1OT1+antagomir NC组和si-KCNQ1OT1+miR-124-3p antagomir组。除Sham组外，其余组大鼠构建DOP模型。罗氏血糖仪测量大鼠空腹血糖（FBG）；酶联免疫吸附法（ELISA）检测血清空腹胰岛素（FINS）水平；双能X线骨密度仪测定大鼠股骨骨密度（BMD）；三点弯曲实验评估大鼠股骨生物力学状况；HE染色观察大鼠股骨病理损伤；免疫组织化学染色检测股骨组织SOCS5蛋白表达；实时荧光定量PCR（RT-qPCR）检测lncRNA KCNQ1OT1、miR-124-3p、SOCS5 mRNA的表达；双荧光素酶报告基因实验、RNA免疫沉淀（RIP）和RNA pull-down实验验证miR-124-3p与lncRNA KCNQ1OT1和SOCS5的关系。结果：相较于Sham组，DOP组大鼠血清FBG、FINS水平及股骨SOCS5阳性表达率升高，股骨BMD、最大载荷、刚度降低，股骨KCNQ1OT1、SOCS5 mRNA表达升高，miR-124-3p表达降低（均P<0.05）。相较于si-NC组，si-KCNQ1OT1组大鼠股骨KCNQ1OT1、SOCS5 mRNA、SOCS5阳性表达率及血清FBG、FINS水平降低，miR-124-3p表达及股骨BMD、最大载荷、刚度升高（均P<0.05）。相较于si-KCNQ1OT1+antagomir NC组，si-KCNQ1OT1+miR-124-3p antagomir组大鼠股骨SOCS5 mRNA表达升高，miR-124-3p表达降低，血清FBG、FINS水平升高，股骨BMD、最大载荷、刚度降低（均P<0.05）。下调miR-124-3p可减弱敲低KCNQ1OT1对DOP大鼠症状的缓解作用。lncRNA KCNQ1OT1、SOCS5与miR-124-3p存在靶向调控关系，lncRNA KCNQ1OT1特异性结合miR-124-3p，而miR-124-3p靶向SOCS5。结论：lncRNA KCNQ1OT1在DOP大鼠中表达上调，敲低KCNQ1OT1可能通过上调miR-124-3p并靶向下调SOCS5对DOP大鼠发挥改善作用。
Abstract:
Objective:To investigate the effect and mechanism of long non-coding RNA (lncRNA) potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) on diabetic osteoporosis (DOP) in rats by regulating suppressor of cytokine signaling 5 (SOCS5) through microRNA (miR)-124-3p.Methods：Seventy-two SD rats were randomly separated into 6 groups (12 per group) using a random number table:Sham group,DOP group,si-NC group,si-KCNQ1OT1 group,si-KCNQ1OT1+antagonist NC group,and si-KCNQ1OT1+miR-124-3p antagonist group.Except for the Sham group,DOP rat models were constructed for the other groups.Roche blood glucose meter was applied to measure FBG in rats.ELISA was applied to measure FINS in rat serum.Dual energy X-ray bone density instrument was applied to measure BMD of the femur in rats.Three-point bending experiment was applied to evaluate the biomechanical status of rat femurs.HE staining was applied to observe pathological damage of rat femur.Immunohistochemical staining was applied to detect the expression of SOCS5 protein in femoral tissue.RT-qPCR was applied to detect the expression of lncRNA KCNQ1OT1,miR-124-3p and SOCS5 mRNA.Dual luciferase reporter gene experiment,RNA immunoprecipitation (RIP) and RNA pull-down experiment were applied to verify the relationship between miR-124-3p and lncRNA KCNQ1OT1,SOCS5.Results:Compared with the Sham group,the levels of serum FBG and FINS and the positive expression rate of SOCS5 in the femur were increased,and the BMD,maximum load and stiffness of the femur were decreased,and the expressions of KCNQ1OT1 and SOCS5 mRNA in the femur were increased,and the expression of miR-124-3p was decreased in the DOP group (all P<0.05).Compared with the si-NC group,KCNQ1OT1,SOCS5 mRNA,SOCS5 positive expression rate in the femur,and serum FBG and FINS levels were decreased,and the expression of miR-124-3p and femur BMD,maximum load and stiffness were increased in the si-KCNQ1OT1 group (all P<0.05).Compared with si-KCNQ1OT1+antagomir NC group,the expression of SOCS5 mRNA in the femur of si-KCNQ1OT1+miR-124-3p antagomir group was increased,the expression of miR-124-3p was decreased,and the levels of serum FBG and FINS were increased,and the BMD,maximum load and stiffness of femur decreased (all P<0.05).Downregulating miR-124-3p was able to weaken the alleviating effect of knocking down KCNQ1OT1 on symptoms in DOP rats.There was a targeted regulatory relationship between lncRNA KCNQ1OT1,SOCS5,and miR-124-3p,lncRNA KCNQ1OT1 specifically bound to miR-124-3p,while miR-124-3p targeted SOCS5.Conclusion:LncRNA KCNQ1OT1 is upregulated in DOP rats,and knocking down KCNQ1OT1 may improve DOP rats by upregulating miR-124-3p and targeting downregulating SOCS5.

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备注/Memo

备注/Memo:
广东省中医药局科研项目（20211232）
更新日期/Last Update: 2025-09-04