MLF1IP通过BRCA1/AKT/p27信号轴促进结直肠癌细胞增殖的机制研究

批准号:
82002919
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
徐玉婷
依托单位:
学科分类:
肿瘤细胞命运
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
徐玉婷
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中文摘要
结直肠癌细胞的快速增殖是造成患者死亡的重要原因之一,但其机制尚不甚明晰。申请者在前期工作中发现MLF1IP能促进结直肠癌细胞增殖;干扰MLF1IP可导致结直肠癌细胞G1/S期阻滞,并上调BRCA1和p27蛋白的表达,而下调p-AKT蛋白的表达;MLF1IP与BRCA1的转录调控密切相关。故推测:MLF1IP通过调控BRCA1/AKT/p27信号轴促进结直肠癌细胞增殖。本项目拟用多种分子生物学手段观察MLF1IP对BRCA1/AKT/p27信号轴的调控作用,并在结直肠癌临床样本及动物模型中检测MLF1IP与BRCA1的表达并探讨其与结直肠癌细胞增殖的相关性。最后,通过RT-PCR、荧光素酶报告实验、ChIP和结合位点突变载体等方法解析MLF1IP与BRCA1启动子的结合效应与作用位点,从而阐明MLF1IP调控BRCA1转录的具体机制。本课题为临床防治结直肠癌提供新的靶点和策略。
英文摘要
The rapid proliferation of colorectal cancer cells is a leading cause of death in colorectal cancer patients, however, the mechanism remains unclear. In the preliminary work, we found that MLF1IP could promote the proliferation of colorectal cancer cells. Furthermore, we found that knockdown of MLF1IP caused G1/S phase arrest in colorectal cancer cells. In MLF1IP-shRNA expressing cells, the expression of BRCA1 and p27 proteins were upregulated, and the expression of p-AKT protein was downregulated. Moreover, MLF1IP was closely associated with transcriptional regulation of BRCA1 gene. Therefore, it is speculated that MLF1IP affects colorectal cancer proliferation through mediating BRCA1/AKT/p27 signaling pathway. On this basis, we intend to observe the effect of MLF1IP on the BRCA1/AKT/p27 signaling pathway by molecular biology methods, and analyze the expression of the MLF1IP and BRCA1 in colorectal cancer clinical samples and animal models and their correlation with the proliferation of colorectal cancer. Finally, binding site of MLF1IP on BRCA1 promoter is verified using RT-PCR, luciferase reporting experiment, ChIP and binding site mutation vectors to illuminate the the specific regulatory mechanism of MLF1IP on BRCA1 gene transcription. This project will provide novel targets and strategies for treatment of colorectal cancer patients.
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
DOI:10.1016/j.cellsig.2022.110273
发表时间:2022-02
期刊:Cellular signalling
影响因子:4.8
作者:Yuting Xu;Lin Zhang;Qingling Wang;Maojin Zheng
通讯作者:Yuting Xu;Lin Zhang;Qingling Wang;Maojin Zheng
DOI:10.1007/s11033-023-08662-4
发表时间:2023-08
期刊:Molecular Biology Reports
影响因子:2.8
作者:Lin Zhang;Yuting Xu;Enmin Cai;Maojin Zheng;Lei Liu;Qingling Wang;Shibao Li
通讯作者:Lin Zhang;Yuting Xu;Enmin Cai;Maojin Zheng;Lei Liu;Qingling Wang;Shibao Li
DOI:10.1016/j.yexcr.2023.113601
发表时间:2023-04
期刊:Experimental cell research
影响因子:3.7
作者:Lin Zhang;Q. Pan;Yi Wu;Peng Zhang;Shibao Li;Yuting Xu;Danhua Li;Maojin Zheng;D. Pei
通讯作者:Lin Zhang;Q. Pan;Yi Wu;Peng Zhang;Shibao Li;Yuting Xu;Danhua Li;Maojin Zheng;D. Pei
国内基金
海外基金
