胆管细胞癌相关RNA编辑的鉴定及其功能机制研究
项目介绍
AI项目解读
基本信息
- 批准号:82002573
- 项目类别:青年科学基金项目
- 资助金额:24.0万
- 负责人:
- 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
- 起止时间:2020 至 2023
- 项目参与者:曹鹏博;
- 关键词:
项目摘要
The intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer (PLC), accounting for 10-15% of all PLCs. Despite the relative low incidence of iCCA, it deserves urgent attention because the worldwide incidence of this malignancy has been increasing steadily and substantially over the past four decades. In addition to genomic alterations, RNA editing is another recently described epigenetic mechanism in which sequence alterations are introduced into the genome-encoded RNA transcripts, while leaving the underlying genome intact and unmodified. To date, however, the role of ADARs and the landscape of RNA-edited targets in iCCA remains unknown. In this study, to gain an insight into the landscape of RNA editing in iCCAs, we performed an integrative whole-exome and transcriptome sequencing analysis on 15 pairs of iCCA tissues and their matched adjacent non-tumor liver tissues. Further, using an exemplary target gene Kip1 ubiquitination-promoting complex 1 (KPC1), we discovered an ADAR1-mediated recoding RNA editing event causing an amino acid substitution from methionine (Met) to valine (Val) at codon 8 of KPC1 (p.M8V). Our preliminary functional studies showed that wide-type KPC1 could significantly suppress the proliferation and migration of cholangiocarcinoma cell lines, while the RNA editing conferred a loss-of-function phenotype. Additionally, KPC1 may act as a tumor suppressor by inhibiting NF-κB pathway. Furthermore, we will determine the tumorigenic roles of the newly identified A-to-I editing of KPC1 by both in vitro and in vivo assays, and then investigate whether and how KPC1 RNA editing affects cell proliferation and migration by regulating NF-κB pathway. The aim of this study is to clarify the molecular mechanism of KPC1 RNA editing in the development of iCCA, and our results may highlight RNA editing as another mechanism of sequence alteration contributing to iCCA progression, and provide potential targets for treatment of this malignancy.
肝内胆管细胞癌(iCCA)约占肝脏原发恶性肿瘤的10%-15%。目前针对iCCA的临床治疗手段极其有限,而且关于其发生进展的分子机制的理解仍非常局限。RNA编辑是遗传信息转录后加工修饰的一种重要形式。目前尚未见在iCCA中关于RNA编辑的研究报道。本研究前期通过开展iCCA转录组和基因组整合分析全面地绘制了RNA编辑图谱,并发现了一个位于E3泛素连接酶KPC1上的新的非同义编辑位点。初步研究发现此编辑位点在iCCA中发生由ADAR1介导的过编辑;KPC1在iCCA细胞中发挥抑癌功能,而其编辑体表现出功能缺失;表达谱分析提示KPC1可能通过参与调控NF-κB信号通路活性发挥抑癌作用。本研究拟在此基础上,深入阐明KPC1 RNA编辑的肿瘤生物学功能、揭示其分子机制并探究其临床相关性。期望通过此研究,从转录后调控层面为阐明iCCA发生发展机理提供理论依据,为防治iCCA的药物研发提供候分子靶标。
结项摘要
项目成果
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
Down-regulation of MYH10 driven by chromosome 17p13.1 deletion promotes hepatocellular carcinoma metastasis through activation of the EGFR pathway.
- DOI:10.1111/jcmm.17036
- 发表时间:2021-12
- 期刊:Journal of cellular and molecular medicine
- 影响因子:5.3
- 作者:Jin Q;Cheng M;Xia X;Han Y;Zhang J;Cao P;Zhou G
- 通讯作者:Zhou G
Identification of senescence-associated long non-coding RNAs to predict prognosis and immune microenvironment in patients with hepatocellular carcinoma.
- DOI:10.3389/fgene.2022.956094
- 发表时间:2022
- 期刊:FRONTIERS IN GENETICS
- 影响因子:3.7
- 作者:Gao, Chengzhi;Zhou, Guangming;Cheng, Min;Feng, Lan;Cao, Pengbo;Zhou, Gangqiao
- 通讯作者:Zhou, Gangqiao
The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50.
- DOI:10.1186/s13046-022-02549-1
- 发表时间:2022-12-08
- 期刊:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
- 影响因子:11.3
- 作者:Gao, Chengming;Zhou, Guangming;Shi, Jie;Shi, Peipei;Jin, Liang;Li, Yuanfeng;Wang, Xiaowen;Liao, Song;Yan, Han;Wu, Junjie;Lu, Yiming;Zhai, Yun;Zhang, Jinxu;Zhang, Haitao;Zhang, Hongxing;Yang, Chenning;Cao, Pengbo;Cheng, Shuqun;Zhou, Gangqiao
- 通讯作者:Zhou, Gangqiao
miR-424-3p promotes metastasis of hepatocellular carcinoma via targeting the SRF-STAT1/2 axis
- DOI:10.1093/carcin/bgad037
- 发表时间:2023-05-26
- 期刊:CARCINOGENESIS
- 影响因子:4.7
- 作者:Feng,Lan;Chen,Xi;Zhou,Gangqiao
- 通讯作者:Zhou,Gangqiao
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:{{ item.doi || "--"}}
- 发表时间:{{ item.publish_year || "--" }}
- 期刊:{{ item.journal_name }}
- 影响因子:{{ item.factor || "--"}}
- 作者:{{ item.authors }}
- 通讯作者:{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:{{ item.authors }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:{{ item.authors }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:{{ item.authors }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:{{ item.authors }}
数据更新时间:{{ patent.updateTime }}
其他文献
长链非编码RNA MALAT1促进肝癌细胞系迁移的机制研究
- DOI:--
- 发表时间:2017
- 期刊:军事医学
- 影响因子:--
- 作者:韩辉;李海北;曹鹏博;秦庚;周钢桥
- 通讯作者:周钢桥
竞争性内源RNA在转录后水平调控基因表达
- DOI:--
- 发表时间:2015
- 期刊:生物物理学报
- 影响因子:--
- 作者:李海北;宋瑾;曹鹏博;周钢桥
- 通讯作者:周钢桥
其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:{{ item.doi || "--" }}
- 发表时间:{{ item.publish_year || "--"}}
- 期刊:{{ item.journal_name }}
- 影响因子:{{ item.factor || "--" }}
- 作者:{{ item.authors }}
- 通讯作者:{{ item.author }}

内容获取失败,请点击重试

查看分析示例
此项目为已结题,我已根据课题信息分析并撰写以下内容,帮您拓宽课题思路:
AI项目摘要
AI项目思路
AI技术路线图

请为本次AI项目解读的内容对您的实用性打分
非常不实用
非常实用
1
2
3
4
5
6
7
8
9
10
您认为此功能如何分析更能满足您的需求,请填写您的反馈:
曹鹏博的其他基金
NCOR1功能缺陷通过促进基因组突变负荷增加肿瘤免疫检查点阻断治疗响应
- 批准号:
- 批准年份:2021
- 资助金额:55 万元
- 项目类别:面上项目
相似国自然基金
{{ item.name }}
- 批准号:{{ item.ratify_no }}
- 批准年份:{{ item.approval_year }}
- 资助金额:{{ item.support_num }}
- 项目类别:{{ item.project_type }}
相似海外基金
{{
item.name }}
{{ item.translate_name }}
- 批准号:{{ item.ratify_no }}
- 财政年份:{{ item.approval_year }}
- 资助金额:{{ item.support_num }}
- 项目类别:{{ item.project_type }}