[1]孔德隆陈彦华** 弭德扬张浩杰陈高鹏.基于lncRNA-miRNA-mRNA调控网络的骨关节炎关键基因筛选与分析及中药预测[J].现代中医药,2024,(04):109-118.[doi:10.13424/j.cnki.mtcm.2024.04.020]
点击复制

基于lncRNA-miRNA-mRNA调控网络的骨关节炎关键基因筛选与分析及中药预测()
分享到:

《现代中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2024年04期
页码:
109-118
栏目:
出版日期:
2024-08-28

文章信息/Info

文章编号:
1672-0571(2024)04-0109-10
作者:
孔德隆1陈彦华2** 弭德扬3张浩杰1陈高鹏1
1.山东中医药大学,山东 济南 250014;
2.山东中医药大学附属医院,山东 济南 250014;
3.济南市章丘区中医医院,山东 济南 250014
关键词:
关键词:lncRNA-miRNA-mRNA骨关节炎关键基因药物预测
分类号:
R274.9
DOI:
10.13424/j.cnki.mtcm.2024.04.020
文献标志码:
A
摘要:
摘 要:目的 通过构建lncRNA-miRNA-mRNA调控网络揭示骨关节炎的关键基因,并预测其潜在治疗药物。方法 从基因表达综合数据库(Gene Expression Omnibus,GEO)数据库获取骨关节炎(Osteoarthritis,OA)和正常骨关节样品差异表达的lncRNA和mRNA,并通过miRDB、miRTarBase、TargetScan数据库预测miRNA,并整合lncRNA-miRNA与miRNA-mRNA表达谱的相互作用,以构建ceRNA网络。将miRNA预测靶基因与差异表达mRNA取交集,构建PPI网络图,并进行GO功能和KEGG通路富集分析。利用Coremine Medical数据库筛选核心靶点预测得到的中药。结果 共鉴定出339个DEmRNA和476个lncRNA。在ceRNA网络中总共获得了4个差异的lncRNA-miRNA相互作用和39个失调的miRNA-mRNA相互作用,包括4个DElncRNA,20个miRNA和39个DEmRNA。PPI网络图鉴定出VEGFA、DDIT4、MMP2、SESN1、VCAN等10个靶点可能是调控骨关节炎的核心靶点。随后的富集分析表明,这些mRNA在OA的发展过程中调节了生物代谢、细胞外基质的组织和免疫反应等生物过程,并丰富了HIF-1信号通路和PI3K-Akt 信号通路。预测得到丹参、郁金、姜黄、黄芪、白花蛇舌草等中药可能是治疗OA 的潜在药物。结论 这项研究为OA中与lncRNA相关的ceRNA网络提供了新颖的见解,丹参、郁金、姜黄、白花蛇舌草可能是治疗OA潜在药物。

参考文献/References:

[1]DU XM,CAI LY,XIE J,et al.The role of TGF-beta3 in cartilage development and osteoarthritis[J].Bone Research,2023,11(1):2.
[2]李强,庞仲辉,陶飞飞,等.萆薢总皂苷通过抑制软骨基质降解改善豚鼠骨关节炎的作用研究[J].现代中医药,2022,42(6):37-41.
[3]TATEBE M,IWATSUKI K,HIRATA H,et al.Effects of depression and inflammatory factors on chronic conditions of the wrist[J].The Bone & Joint Journal,2016,98-B(7):961-968.
[4]WU J,LI HL,HU F,et al.Stevioside attenuates osteoarthritis via regulating Nrf2/HO-1/NF-κB pathway[J].Journal of Orthopaedic Translation,2022,38:190-202.
[5]GóMEZ R,CONDE J,SCOTECE M,et al.What’s new in our understanding of the role of adipokines in rheumatic diseases?[J].Nature Reviews Rheumatology,2011,7(9):528-536.
[6]YAO N,PENG S,WU H,et al.Long noncoding RNA PVT1 promotes chondrocyte extracellular matrix degradation by acting as a sponge for miR-140 in IL-1β-stimulated chondrocytes[J].Journal of Orthopaedic Surgery and Research,2022,17(1):218.
[7]RAI MI,ALAM M,LIGHTFOOT DA,et al.Classification and experimental identification of plant long non-coding RNAs[J].Genomics,2019,111(5):997-1005.
[8]LIU YB,LIN LP,ZOU R,et al.MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis[J].Cell Cycle,2018,17(21/22):2411-2422.
[9]CROSS M,SMITH E,HOY D,et al.The global burden of hip and knee osteoarthritis:estimates from the global burden of disease 2010 study[J].Annals of the Rheumatic Diseases,2014,73(7):1323-1330.
[10]康朝宾,赵亚妮,卢延荣.温针灸联合灯盏细辛穴位注射治疗类风湿性关节炎临床研究[J].现代中医药,2022,42(6):117-121.
[11]FELLOWS CR,MATTA C,MOBASHERI A.Applying proteomics to study crosstalk at the cartilage-subchondral bone interface in osteoarthritis:current status and future directions[J].EBioMedicine,2016,11:2-4.
[12]LUI JC,GARRISON P,NGUYEN Q,et al.EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy[J].Nature Communications,2016,7:13685.
[13]HE CL,GAO H,FAN XN,et al.Identification of a novel miRNA-target gene regulatory network in osteosarcoma by integrating transcriptome analysis[J].International Journal of Clinical and Experimental Pathology,2015,8(7):8348-8357.
[14]KNUDSON CB,KNUDSON W.Cartilage proteoglycans[J].Seminars in Cell & Developmental Biology,2001,12(2):69-78.
[15]CS-SZAB G,MELCHING LI,ROUGHLEY PJ,et al.Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples[J].Arthritis and Rheumatism,1997,40(6):1037-1045.
[16]LI HZ,XU XH,LIN N,et al.Overexpression of miR-10a-5p facilitates the progression of osteoarthritis[J].Aging,2020,12(7):5948-5976.
[17]CAI HQ,MIAO MY,WANG ZG.MiR-214-3p promotes the proliferation,migration and invasion of osteosarcoma cells by targeting CADM1[J].Oncology Letters,2018,16(2):2620-2628.
[18]SOPHIA FOX AJ,BEDI A,RODEO SA.The basic science of articular cartilage:structure,composition,and function[J].Sports Health,2009,1(6):461-468.
[19]SAITO T,FUKAI A,MABUCHI A,et al.Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development[J].Nature Medicine,2010,16(6):678-686.
[20]AL-MODAWI RN,BRINCHMANN JE,KARLSEN TA.Multi-pathway protective effects of microRNAs on human chondrocytes in an in vitro model of osteoarthritis[J].Molecular Therapy Nucleic Acids,2019,17:776-790.
[21]WANG YJ,SHEN SP,LI Z,et al.MIR-140-5p affects chondrocyte proliferation,apoptosis,and inflammation by targeting HMGB1 in osteoarthritis[J].Inflammation Research,2020,69(1):63-73.
[22]LAFONT JE,TALMA S,HOPFGARTEN C,et al.Hypoxia promotes the differentiated human articular chondrocyte phenotype through SOX9-dependent and-independent pathways[J].The Journal of Biological Chemistry,2008,283(8):4778-4786.
[23]SHAO J,ZHANG Y,YANG TY,et al.HIF-1α disturbs osteoblasts and osteoclasts coupling in bone remodeling by up-regulating OPG expression[J].In Vitro Cellular & Developmental Biology-Animal,2015,51(8):808-814.
[24]XUE JF,SHI ZM,ZOU J,et al.Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis[J].Biomedecine & Pharmacotherapie,2017,89:1252-1261.
[25]LIU SY,CAO CX,ZHANG YJ,et al.PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis[J].Journal of Orthopaedic Surgery and Research,2019,14(1):425.
[26]李曼,张露蓉.中药白花蛇舌草抗炎作用研究进展[J].辽宁中医药大学学报,2021,23(10):164-167.
[27]孙林林,乔利,田振华,等.姜黄化学成分及药理作用研究进展[J].山东中医药大学学报,2019,43(2):207-212.
[28]刘梅,郭小红,孙全,等.温郁金的化学成分和药理作用研究进展[J].现代药物与临床,2021,36(1):204-208.
[29]张建业,张卫华,韩俊,等.丹参酮ⅡA抑制软骨细胞炎症、软骨基质降解的机制及对大鼠骨关节炎的影响[J].解放军医药杂志,2021,33(3):10-16.
[30]张金锋,徐志龙,吴梦,等.丹参酮ⅡA通过抑制信号通路延缓膝骨关节炎大鼠软骨退变及抑制局部炎症的研究[J].中国药学杂志,2021,56(23):1918-1926.
[31]骞立刚,孙博,于泊,等.丹酚酸B减轻骨关节炎模型大鼠软骨组织损伤[J].基础医学与临床,2023,43(1):159-164.
[32]KUPTNIRATSAIKUL V,DAJPRATHAM P,TAECHAARPORNKUL W,et al.Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis:a multicenter study[J].Clinical Interventions in Aging,2014,9:451-458.
[33]SUN YF,LIU W,ZHANG H,et al.Curcumin prevents osteoarthritis by inhibiting the activation of inflammasome NLRP3[J].Journal of Interferon & Cytokine Research,2017,37(10):449-455.
[34]李亚楠,倪娟,方禹舜,等.姜黄素通过调控脂多糖诱导的炎症抑制软骨细胞凋亡[J].中成药,2021,43(7):1904-1908.
[35]HAN GT,ZHANG YB,LI HH.The combination treatment of curcumin and probucol protects chondrocytes from TNF-α induced inflammation by enhancing autophagy and reducing apoptosis via the PI3K-akt-mTOR pathway[J].Oxidative Medicine and Cellular Longevity,2021,2021:5558066.

相似文献/References:

[1]吴磊磊张俊忠.基于网络药理学的桃红四物汤治疗 骨关节炎作用机制研究[J].现代中医药,2021,(05):024.[doi:10.13424/j.cnki.mtcm.2021.05.005]
 WU LeileiZHANG Junzhong.Study on The Mechanism of Taohong Siwu Decoction in The Treatment of Osteoarthritis Based on Network Pharmacology[J].Modern Traditional Chinese Medicine,2021,(04):024.[doi:10.13424/j.cnki.mtcm.2021.05.005]

备注/Memo

备注/Memo:
基金项目:山东省中医药科技发展计划项目(2019-0113);山东省中医药科技项目(2020Q016)
更新日期/Last Update: 2024-07-15