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LncRNA-SNHG6活化NF-κB通路促进骨肉瘤发病转移及益气化瘀清热解毒法的疗效机制研究

LncRNA-SNHG6活化NF-κB通路促进骨肉瘤发病转移及益气化瘀清热解毒法的疗效机制研究
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  • 批准号:81674006
  • 批准年度: 2016年
  • 学科分类:中医骨伤科(H2710) |
  • 项目负责人:杨燕萍
  • 负责人职称:研究员
  • 依托单位:上海中医药大学
  • 资助金额:64万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: LncRNA-SNHG6;NF-κB;骨肉瘤;化瘀;清热解毒法
  • 英文关键词:LncRNA;SNHG6;Osteosarcoma;NF-κB;Qichong sanchi pulvis

项目摘要

中文摘要

骨肉瘤是儿童青少年最常见恶性肿瘤,转移后5年存活率不足30%,诊断时是否伴肺转移是预测5年存活率关键指标。.长链非编码RNA是新发现的癌症调控因子,作为效应分子能更好标记肿瘤特征,针对它的治疗副作用较少,但其对骨肉瘤调控作用不清楚。NF-κB参与肿瘤发病的各个环节,针对该通路的靶向治疗是提高抗癌药物对骨肉瘤活性的有效方法。芯片检测发现人骨肉瘤组织中长链非编码RNA-SNHG6、NF-κB通路关键因子Ikkβ和XIAP显著上调。.本项目用CRISPR/Cas9技术敲除骨肉瘤细胞中SNHG6基因,在野生型及SNHG6敲除骨肉瘤细胞、原位和肺转移裸鼠骨肉瘤、SNHG6敲入小鼠模型中运用RT-PCR、Northern Blot、RIP、RNA EMSA、原位杂交、免疫组化等方法研究,揭示SNHG6激活NF-κB通路对骨肉瘤发病和转移的重要性,以及“芪重三七散”体内外抗骨肉瘤发病和肺转移的效应机制。

英文摘要

Osteosarcoma is a most common cancer in children and adolescents, the 5-year survival rate is less than 30% with metastasis. With pulmonary metastasis or not at diagnosis is the key prognosis indicator of the 5-year survival rate. .Long non-coding RNAs (lncRNAs) are newly discovered cancer regulatory factors, and can preferably mark the tumor inherent characteristics as the effector molecules, treatment targets lncRNAs will have fewer side effects, but their regulatory roles in osteosarcoma are not clear. NF-κB signaling is involved in many aspects of cancer incidence, and anticancer therapy targeted NF-κB pathway is an effective strategy for improving the activity of anti-osteosarcoma drugs. Expression of SNHG6 (lncRNA), Ikkβ and XIAP (NF-κB pathway critical factors) was significantly upregulated in human osteosarcoma tissues detected by lncRNAs microarray..In this project, SNHG6 gene knockout osteosarcoma cells will be generated by the CRISPR/Cas9 technique. RT-PCR, Northern Blot, RIP, RNA EMSA, in situ hybridization, immunohistochemistry, and other techniques will be used to study and reveal the importance of NF-κB activated by SNHG6 in osteosarcoma incidence and metastasis, and the effective mechanisms of "Qichong sanchi pulvis " for anti-osteosarcoma incidence and lung metastasis in vivo, with the models of wild-type and SNHG6 knockout osteosarcoma cells, in situ and lung metastasis osteosarcoma nude mice, SNHG6 knock-in mice.

评估说明

    国家自然科学基金项目“LncRNA-SNHG6活化NF-κB通路促进骨肉瘤发病转移及益气化瘀清热解毒法的疗效机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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