课题基金基金详情
外泌体lncRNAuc002ktr.3在肺鳞癌顺铂耐药中的作用及其作为新型耐药标志物的临床价值
结题报告
批准号:
81972006
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
王保龙
依托单位:
学科分类:
分子生物学检验
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王保龙
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中文摘要
长链非编码RNA(lncRNA)广泛参与肿瘤增殖、转移和耐药等生物学过程。外泌体内含多种生物活性物质可传递耐药性,且被认为是理想的液态活检材料。我们前期研究发现,lnc-uc002ktr.3(ktr.3)在肺鳞癌顺铂耐受中起关键作用,但其机制尚不清楚。生信学预测ktr.3的DNA能与转录因子sMaf和Bach1发生作用,而sMaf可与MIB1启动子结合。MIB1是Wnt通路活化剂和Notch通路配体。据此我们推测:ktr.3与其DNA形成杂合体以“分子支架”形式招募sMaf和Bach1,促进MIB1转录,激活Notch和Wnt通路介导顺铂耐受。本课题拟从细胞、动物和临床等层面研究ktr.3在顺铂耐受中的作用及其机制;确定ktr.3可通过外泌体传递介导顺铂耐受;探讨血浆外泌体ktr.3在预测肺鳞癌顺铂耐受及疗效监测中的临床价值。本研究将为肺鳞癌的精准化疗和疗效监测提供新的标志物。
英文摘要
Long non-coding RNA (LncRNA) is widely involved in biological processes such as tumor proliferation, metastasis and drug resistance. Exosomes, which contain a variety of bio-active substances, are involved in drug resistance and are considered to be the ideal liquid biopsy materials. Our previous study found that lnc-uc002ktr.3(ktr.3) plays a key role in cisplatin resistance of lung squamous cell carcinoma, but its mechanism is still unclear. Bio-informatics predicted that DNA of ktr.3 could interact with transcription factors sMaf and Bach1. Moreover, sMaf could bind to MIB1 promoter. MIB1 is a Wnt-pathway activator and Notch-pathway ligand. Therefore, we proposed a hypothesis that ktr.3 forms a hybrid with its DNA to recruit sMaf and Bach1 in the form of "molecular scaffold", which promotes the transcription of MIB1, and activates Notch and Wnt pathways to mediate the drug resistance of cisplatin. This study will investigate the role and mechanism of ktr.3 in cisplatin resistance from the aspect of cells, animals and clinical results and determine that ktr.3 could mediate cisplatin resistance through exosome transmitted. Moreover, this study will investigate the clinical value of plasma exosome ktr.3 in the prediction of cisplatin resistance and the monitoring of therapeutic effect in lung squamous cell carcinoma. This study will provide new biomarkers for the accurate chemotherapy and efficacy monitoring of lung squamous cell carcinoma.
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