环状RNA-104871/miR-140-3p/SIRT1轴促进RA滑膜成纤维细胞增殖迁移的机制研究
结题报告
批准号:
81771747
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
杨敏
依托单位:
学科分类:
H1107.自身免疫性疾病
结题年份:
2021
批准年份:
2017
项目状态:
已结题
项目参与者:
欧阳晴晴、任昊、赵进军、黄琴、朱俊卿、朱丁季、江珍兰
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中文摘要
实验发现circRNA_104871在RA滑膜成纤维细胞(FLS)和外周血单个核细胞中均表达升高。在RA FLS中过表达circRNA_104871,FLS增殖迁移能力增加,但机制未明。生物信息学分析发现circRNA_104871有miR-140-3p结合位点,实验发现miR-140-3p在RA FLS中表达降低。在RA FLS中过表达circRNA_104871,miR-140-3p表达下降,说明circRNA_104871可能通过吸附miR-140-3p起作用。研究表明沉默信息调节因子1(SIRT1)在RA FLS表达升高并可促进RA FLS增殖迁移,且有研究者在软骨细胞中证明了SIRT1是miR-140-3p一个直接靶基因。因此我们推测circRNA_104871可能通过吸附miR-140-3p调控SIRT1促进RA FLS增殖迁移。该机制的阐明可为RA治疗药物的研发提供新思路。
英文摘要
Our study identified that the expression of circRNA_104871 were both upregulated in RA fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cell compared to controls. Overexpression of circRNA_104871 could enhance the proliferation and migration of RA FLS, however, the mechanism was unknown yet. We found that circRNA_104871 sequence contained a binding site of miR-140-3p by bioinformatics analysis. In our study, we found that the expression of miR-140-3p was significantly lower in RA FLS than osteoarthritis FLS, and overexpression of circRNA_104871 could diminish miR-140-3p expression, which demonstrated that circRNA_104871 may functions as a competitive endogenous RNA to sponge miR-140-3p. Study showed that the expression of silent information regulator 1(SIRT1) were increased in RA FLS than OA FLS and overexpression of SIRT1 could accelerate the proliferation and migration of RA FLS. Research showed that SIRT1 was a direct target of miRNA-140-3p. Thus, we suggested that circRNA_104871 may function as a competitive endogenous RNA to promote the proliferation and migration of FLS by regulating SIRT1 expression through sponging miR-140-3p in RA. The elucidation of the mechanism can provide new target for the development of RA drugs.
没有研究报道环状RNA在类风湿关节炎(RA)中的作用。试验发现circ_104871在RA滑膜成纤维细胞(FLS)和外周血单个核细胞中表达升高,在RAFLS中过表达circ_104871,FLS增殖迁移能力增加,但其机制未明。生物信息学分析发现circ_104871序列上有miR-140-3p结合位点,试验发现miR-140-3p在RA FLS表达与OA相比显著降低,在RA FLS过表达circ_104871,miR-140-3p表达下降。说明circ_104871可能通过吸附miR-140-3p起作用。研究表明沉默信息调节因子1(SIRT1)3′UTR端有miR-140-3p的结合位点,两者可直接相互作用。SIRT1在RAFLS的表达升高并可促进RAFLS增殖和迁移。因此我们推测circ_104871可能通过吸附miR-140-3p调控SIRT1促进RAFLS的增殖和迁移。.该项目实验已基本完成,circRNA_10487在circBase里的命名为circ_0088036,我们实验证明circRNA_10487(circ_0088036)以竞争性内源RNA的方式结合miR-140-3p调控SIRT1进而促进 RA滑膜成纤维细胞增殖和迁移,相关数据发表在Molecular Immunology (IF=3.641)。.另外我们通过单细胞测序检测了干燥综合征外周PBMC,探索了血CD4+细胞毒性T细胞参与自身免疫病的研究,相关文章发表在Frontiers in Immunology(IF=5.085)。.最后我们通过芯片及后续的验证实验发现一个新的circRNA—circ_0088194在RA滑膜成纤维细胞中表达升高,并且通过实验证明了circ_0088194可通过miR-776-3p/MMP轴促RA滑膜成纤维细胞迁移和侵袭,相关文章发表在Frontiers in Immunology(IF=5.085)。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.
Circ_0088194 通过 miR-766-3p/MMP2 轴促进类风湿关节炎成纤维细胞样滑膜细胞的侵袭和迁移
DOI:10.3389/fimmu.2021.628654
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Cai Y;Liang R;Xiao S;Huang Q;Zhu D;Shi GP;Ouyang Q;Yang M
通讯作者:Yang M
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.
单细胞 RNA 测序揭示了原发性干燥综合征中细胞毒性 CD4 T 淋巴细胞的扩增和免疫细胞的情况
DOI:10.3389/fimmu.2020.594658
发表时间:2020
期刊:Frontiers in immunology
影响因子:7.3
作者:Hong X;Meng S;Tang D;Wang T;Ding L;Yu H;Li H;Liu D;Dai Y;Yang M
通讯作者:Yang M
Hsa_circ_0088036 promotes the proliferation and migration of fibroblast-like synoviocytes by sponging miR-140-3p and upregulating SIRT 1 expression in rheumatoid arthritis
Hsa_circ_0088036 通过海绵 miR-140-3p 和上调 SIRT 1 表达促进类风湿关节炎中成纤维样滑膜细胞的增殖和迁移
DOI:10.1016/j.molimm.2020.07.004
发表时间:2020
期刊:Molecular Immunology
影响因子:3.6
作者:Zhong Shuping;Ouyang Qingqing;Zhu Dingji;Huang Qin;Zhao Jinjun;Fan Meida;Cai Yujie;Yang Min
通讯作者:Yang Min
组织蛋白酶S在早期RA中的作用:一个潜在的治疗新靶点
  • 批准号:
    81172875
  • 项目类别:
    面上项目
  • 资助金额:
    60.0万元
  • 批准年份:
    2011
  • 负责人:
    杨敏
  • 依托单位:
滑膜肥大细胞对成纤维细胞Cathepsins和MMPs的影响:"类风湿性关节炎治疗的新靶点"
  • 批准号:
    30972747
  • 项目类别:
    面上项目
  • 资助金额:
    30.0万元
  • 批准年份:
    2009
  • 负责人:
    杨敏
  • 依托单位:
国内基金
海外基金