乏氧诱导的EDI3通过线粒体自噬调控三阴性乳腺癌化疗耐药及进展转移的机制研究

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中文摘要
三阴性乳腺癌是预后较差的分子亚型,化疗耐药及进展转移是影响其预后的主要因素,探讨三阴性乳腺癌化疗耐药及转移的分子机制是乳腺肿瘤学界研究的热点。肿瘤微环境影响着肿瘤的生物学行为,乏氧是肿瘤微环境的重要特征之一,研究证实三阴性乳腺癌与乳腺癌其他分子亚型相比乏氧特征更为显著。我们前期工作发现乏氧可诱导三阴性乳腺癌的线粒体自噬,并利用RNA-seq高通量测序技术及CRISPR/Cas9-mt-Keima线粒体自噬评价体系筛选出EDI3,确立其是乏氧诱导线粒体自噬的重要调控基因。我们拟进一步通过体内外实验探究乏氧诱导的EDI3调控三阴性乳腺癌化疗耐药及转移的分子机制,并利用组织标本分析其临床应用价值。本项目从肿瘤乏氧微环境角度入手,阐明EDI3通过线粒体自噬调控三阴性乳腺癌化疗耐药和转移的分子机制,为三阴性乳腺癌的治疗提供潜在的分子靶标,也将为三阴性乳腺癌的预后评价提供重要的分子标志物。
英文摘要
Triple negative breast cancer (TNBC) is a subtype with poor prognosis, which is mainly affected by chemotherapy resistance,tumor progression and metastasis. The molecular mechanism of chemoresistance and metastasis of TNBC is a hotspot in the field of breast oncology. Tumor microenvironment plays a key role in modulating the biological behavior of tumors, of which hypoxia is one of the important features. It has been reported that hypoxia is more prominent in TNBC than other molecular subtypes of breast cancer. Our previous work found that hypoxia can induce mitophagy in TNBC, and we screened out EDI3 as an important gene in hypoxia-induced mitophagy with application of high-throughput sequencing and CRISPR/Cas9-mt-Keima mitochondrial autophagy evaluation system. We intend to further explore the molecular mechanism of hypoxia-induced EDI3 in regulation of chemoresistance and metastasis of TNBC by in vitro and in vivo experiments, and analyze its clinical value by tissue samples. This project intends to clarify the molecular mechanism of EDI3-induced mitophagy in the regulation TNBC chemoresistance and metastasis, from the perspective of hypoxic microenvironment. Our project may provide a potential molecular target and a prognostic evaluation marker for the treatment of TNBC.
期刊论文列表
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DOI:10.1080/15548627.2023.2182482
发表时间:2023-03-03
期刊:AUTOPHAGY
影响因子:13.3
作者:Liu, Ying;Zhang, Hanwen;Yang, Qifeng
通讯作者:Yang, Qifeng
Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer.
DOI:10.1155/2021/5529106
发表时间:2021
期刊:Disease markers
影响因子:--
作者:Zhao W;Li X;Wang W;Chen B;Wang L;Zhang N;Wang Z;Yang Q
通讯作者:Yang Q
Fatostatin in Combination with Tamoxifen Induces Synergistic Inhibition in ER-Positive Breast Cancer
Fatostatin 与他莫昔芬联合对 ER 阳性乳腺癌产生协同抑制作用
DOI:10.2147/dddt.s253876
发表时间:2020-01-01
期刊:DRUG DESIGN DEVELOPMENT AND THERAPY
影响因子:4.8
作者:Liu, Ying;Zhang, Ning;Yang, Qifeng
通讯作者:Yang, Qifeng
DOI:10.1002/advs.202204988
发表时间:2023-04
期刊:ADVANCED SCIENCE
影响因子:15.1
作者:Liu, Ying;Liu, Yiwei;He, Yinqiao;Zhang, Ning;Zhang, Siyue;Li, Yaming;Wang, Xiaolong;Liang, Yiran;Chen, Xi;Zhao, Weijing;Chen, Bing;Wang, Lijuan;Luo, Dan;Yang, Qifeng
通讯作者:Yang, Qifeng
The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.
E3 连接酶 TRIM4 促进 SET 泛素介导的降解,增强乳腺癌中 ER-α 的作用。
DOI:10.1002/advs.202201701
发表时间:2022-09
期刊:ADVANCED SCIENCE
影响因子:15.1
作者:Han, Dianwen;Wang, Lijuan;Long, Li;Su, Peng;Luo, Dan;Zhang, Hanwen;Li, Zheng;Chen, Bing;Zhao, Wenjing;Zhang, Ning;Wang, Xiaolong;Liang, Yiran;Li, Yaming;Hu, Guohong;Yang, Qifeng
通讯作者:Yang, Qifeng
GABPA通过调控内源性逆转录病毒表达影响三阴性乳腺癌PD-L1单抗治疗敏感性的作用及机制研究
- 批准号:82373267
- 项目类别:面上项目
- 资助金额:49万元
- 批准年份:2023
- 负责人:张宁
- 依托单位:
新旧动能转换促进城市高质量发展研究:驱动机理、作用路径与提升策略
- 批准号:--
- 项目类别:重点项目
- 资助金额:210万元
- 批准年份:2020
- 负责人:张宁
- 依托单位:
脂代谢相关基因SREBP1调控乳腺癌进展转移及其机制的研究
- 批准号:81502285
- 项目类别:青年科学基金项目
- 资助金额:20.0万元
- 批准年份:2015
- 负责人:张宁
- 依托单位:
国内基金
海外基金
