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Circ_0050102调控miR-1182/NPSR1及MAPK在胰腺癌中的机制研究

批准号:
81902517
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
花苏榕
学科分类:
肿瘤表观遗传
结题年份:
2022
批准年份:
2019
项目状态:
已结题
项目参与者:

项目摘要

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中文摘要
胰腺导管腺癌(PC)严重威胁人类健康。环形RNA和微小RNA相互作用并调控多种肿瘤的增殖分化和凋亡,可作为肿瘤标志物及治疗靶点,但尚未在PC中深入研究。前期工作中,我们基于基因芯片结果选出差异表达显著的circ_0050102,通过生信分析和文献查阅提出"circ_0050102调控miR-1182/NPSR1及下游MAPK通路影响PC发生发展"这一假设。预实验中:用QRT-PCR证实了circ_0050102在PC组织中高表达;体外细胞试验发现敲低其表达后PC细胞增殖能力减弱,迁移侵袭受到抑制,细胞周期阻滞及凋亡率明显增加。实验也证实了circ_0050102、miR-1182与NPSR1之间的相互联系。后续研究将测试circ_0050102吸附miR-1182调控NPSR1及下游MAPK通路这一假设,并进一步探索该途径对PC发生发展的影响,最后通过裸鼠成瘤实验在体内进行验证。
英文摘要
Pancreatic ductal adenocarcinoma (PC) is a serious threat to human health. Circular RNA and microRNA interact and regulate the proliferation, differentiation and apoptosis of various tumors. They can be used as tumor markers and therapeutic targets, but they have not been further studied in PC. In the previous work, we selected circ_0050102 for its significant differential expression from microarray analysis. Through bioinformatics analysis and literature review, we proposed the hypothesis that circ_0050102 regulates the miR-1182/NPSR1 pathway and downstream MAPK pathway to affect the development of PC. In the preliminary experiment, qRT-PCR was utilized for detecting the expression of circ_0050102 in PC tumor tissues. CCK-8 assay, cloning formation assay, transwell assay, flow cytometry were employed for in vitro validation of the effects of circ_0050102 on cell proliferation, cell migration and invasion, cell cycle and cell apoptosis in PC. The correlation between circ_0050102, miR-1182 and NPSR1 was also confirmed. Follow-up studies will test the hypothesis that circ_0050102 adsorbs miR-1182 regulates NPSR1 and downstream MAPK pathway, and further explore the effect of this pathway on the development of PC. The hypothesis will be verified in vivo by nude mice tumorigenesis.
胰腺癌是世界上死亡率最高的肿瘤之一,其5年总生存率约为9%,在过去几十年中,人们一直致力于寻找胰腺癌的早期诊断和治疗方法。竞争性内源性RNA是基因表达的一种新的特异性调控机制,相关研究表明,其在肿瘤的发生、发展调控中可能起到了重要的作用。在这项研究中,我们探索了circ-0050102在胰腺癌组织中的表达及其对肿瘤恶性表型的影响,并进一步研究了circ-00250102、miR-1182和NPSR1之间的相互作用关系。实时定量PCR结果显示胰腺癌组织中circ-00250102表达高于周围正常组织。在细胞功能实验中,circ-0050102表达的下调可以抑制PANC-1和CFPAC-1胰腺癌细胞株的增殖、迁移和侵袭能力,促进细胞凋亡并阻滞细胞周期。此外,在裸鼠的动物实验中,采用同种异体移植后比较的方法,结果表明,circ-0050102表达的抑制可以减缓体内肿瘤的形成。机制研究表明,circ-0050102可以下调miR-1182,而miR-1182不能影响circ-00501 02的表达,且miR-1182可以直接靶向NPSR1并对其进行抑制。此外,circ-0050102可以逆转si-NPSR1对胰腺癌细胞的作用。总之,我们发现circ-0050102可以通过调节miR-1182/NSPR1通路,在促进胰腺癌的发生、发展中发挥了重要作用。
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The promoting effects of hsa_circ_0050102 in pancreatic cancer and the molecular mechanism by targeting miR-1182/NPSR1
hsa_circ_0050102对胰腺癌的促进作用及靶向miR-1182/NPSR1的分子机制
DOI: 10.1093/carcin/bgaa130
发表时间: 2021-01-09
期刊: CARCINOGENESIS
影响因子: 4.7
作者: [Hua, Surong, Gao, Junyi, Liao, Quan]
通讯作者: Liao, Quan
国内基金
海外基金