circFADS2在TCF7L2转录调控下通过miR-876-3p/JAG2 轴和Notch信号通路促进结直肠癌侵袭和转移的分子机制

批准号:
81960432
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
曾元凤
依托单位:
学科分类:
肿瘤复发与转移
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
曾元凤
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中文摘要
circFADS2是我们芯片筛选出的结直肠癌候选circRNA,目前未见其表达及功能研究报道。预实验中我们发现circFADS2能促进结直肠癌细胞体外增殖和侵袭;根据生物信息学分析及预实验结果,我们提出circFADS2表达调控及作用机制,即circFADS2受TCF7L2转录调控,通过吸附miR-876-3p上调JAG2表达并活化Notch信号通路,促进结直肠癌侵袭和转移。本项目拟采用circFADS2过表达和干扰、荧光素酶报告系统、ChIP、RNA pull-down、AGO2-RIP、体内外实验及临床病理分析等,(1)确认TCF7L2是FADS2上游转录因子;(2)确认circFADS2通过ceRNA机制调控miR-876-3p/JAG2轴,促进结直肠癌侵袭和转移。旨在揭示circFADS2表达调控机制,阐明其在结直肠癌进展中的作用,为临床结直肠癌诊治提供新标志物及药物靶点。
英文摘要
CircFADS2 is a candidate circRNA for colorectal cancer tissue screened by our circRNA chip. So far, no studies on its expression and function have been reported. We found circFADS2 promoted colorectal cancer cell proliferation and invasion in our previous study. Based on the bioinformatic analyses and pre-experiment, we proposed a regulatory mechanism of circFADS2 expression and its effect on colorectal cancer cells, that circFADS2, transcriptionally regulated by TCF7L2, upregulates JAG2 by sponging microRNA-876-3p and activates Notch signal pathway to promote invasion and metastasis of colorectal cancer. To validate this mechanism, circFADS2 transfection and interference, luciferase reporter system, chromatin immunoprecipitation (ChIP), RNA pull-down, RNA immunoprecipitation based on AGO2 (AGO2-RIP), experiments in vivo and in vitro, and clinicopathological analyses will be performed (1) to confirm that circFADS2 is targeted by transfection factor TCF7L2, (2) to confirm that circFADS2 upregulates JAG2 by sponging microRNA-876-3p and activates Notch signal pathway to promote invasion and metastasis of colorectal cancer. The aim of this study was to reveal the regulatory mechanism of circFADS2 expression, clarify the role of circFADS2 in the progression of colorectal cancer, and provide new markers and drug targets for clinical diagnosis and treatment of colorectal cancer.
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DOI:10.1177/1535370220929965
发表时间:2020-06-02
期刊:EXPERIMENTAL BIOLOGY AND MEDICINE
影响因子:3.2
作者:Xiao, Yi-Sheng;Tong, Hua-Zhang;Zeng, Yuan-Feng
通讯作者:Zeng, Yuan-Feng
FMNL3基因在结直肠癌转移中的作用及其信号转导通路
- 批准号:81201972
- 项目类别:青年科学基金项目
- 资助金额:23.0万元
- 批准年份:2012
- 负责人:曾元凤
- 依托单位:
国内基金
海外基金
