长链非编码RNA介导氨基酸及脂质代谢重编程在肝癌发生发展过程中作用的研究

批准号:
U19A2008
项目类别:
联合基金项目
资助金额:
247.0 万元
负责人:
刘连新
依托单位:
学科分类:
肿瘤学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
刘连新
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中文摘要
肝癌是消化系统常见恶性肿瘤之一,其生长快速且易发生转移,多预后不良,近年发现肿瘤细胞存在氨基酸及脂质代谢异常,而氨基酸和脂质代谢重编程对肝癌生长转移的作用机制不明。长链非编码RNA(lncRNA)参与包括肿瘤生长在内多种疾病过程调控,我们利用lncRNA芯片筛选,结合生物信息学分析,找到与肝癌预后相关的15个lncRNA,再结合氨基酸代谢调控关键酶,最终筛选出了7个LncRNA。另外,前期实验证明lncRNA-NEAT1 可以通过 ATGL 及其产物甘油一酯和自由脂肪酸促进肝癌的增殖。由此我们猜想,LncRNA通过调控氨基酸及脂质代谢重编程进而调控肝癌的生长转移。本课题中,我们将通过高脂、高糖及高胆固醇饮食或正常饮食结合CCL4诱导形成的肝脏肿瘤模型筛选可能影响脂代谢进而调控肝癌发生发展的差异lncRNA进行深入的功能学分析。本课题拟以上述LncRNA为研究对象,利用RNA免疫共沉淀、肝脏自发肿瘤形成及裸鼠原位肝癌模型等方法,从分子、细胞及动物水平多层面研究LncRNA对肝癌生长、转移及氨基酸和脂质代谢的调控,课题拟从代谢重编程方面探讨肝癌发生发展的机制,率先从氨基酸及脂质代谢重编程角度为肝癌的预防及治疗提供新的思路与借鉴。
英文摘要
Hepatocellular carcinoma (HCC) is one of the common malignant tumors of the digestive system. It grows rapidly and is prone to metastasis, and has a poor prognosis. It has been found that tumor cells have abnormal amino acid and lipid metabolism in recent years, while the mechanism of amino acid and lipid metabolism reprogramming on HCC metastasis is unknown. Long non-coding RNA (lncRNA) is involved in the regulation of various disease processes including tumor growth. We used lncRNA high-throughput sequencing combined with bioinformatics analysis to find 15 lncRNAs related to the prognosis of HCC patients, and combined with key enzymes that regulate amino acid metabolism, Finally, 7 lncRNAs were confirmed to be associated with amino acid metabolism. In addition, previous experiments have shown that lncRNA-NEAT1 promotes HCC proliferation through ATGL and its products, monoglycerides and free fatty acids. From this we hypothesize that LncRNA regulates the growth and metastasis of HCC by regulating amino acid and lipid metabolism reprogramming. In this topic, we will use high-fat, high-sugar and high-cholesterol diets or normal diets combined with CCL4 to induce liver tumor models to screen for differential lncRNAs that may affect lipid metabolism and thus regulate the development of HCC for in-depth functional analysis. This project intends to use the above-mentioned LncRNA as the research object, using RNA immunoprecipitation, spontaneous tumor formation in the liver, and a model of orthotopic HCC in nude mice to study the growth, metastasis, amino acid and Regarding the regulation of lipid metabolism, the subject intends to explore the mechanism of HCC development from the perspective of metabolic reprogramming. It will be the first to provide new ideas and references for the prevention and treatment of HCC from the perspective of amino acid and lipid metabolism reprogramming.
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科研奖励列表
会议论文列表
专利列表
DOI:10.1038/s41388-022-02551-z
发表时间:2022-12-06
期刊:ONCOGENE
影响因子:8
作者:Liu, Yufeng;Sun, Linmao;Liu, Lianxin
通讯作者:Liu, Lianxin
DOI:10.1002/advs.202201210
发表时间:2022-10
期刊:ADVANCED SCIENCE
影响因子:15.1
作者:Zhang, Ben;Thorne, Rick Francis;Zhang, Pengfei;Wu, Mian;Liu, Lianxin
通讯作者:Liu, Lianxin
DOI:10.1016/j.jhep.2023.01.011
发表时间:2023-03-15
期刊:JOURNAL OF HEPATOLOGY
影响因子:25.7
作者:Liu, Yao;Xun, Zhenzhen;Liu, Lianxin
通讯作者:Liu, Lianxin
DOI:10.1186/s13046-022-02547-3
发表时间:2022-12-07
期刊:JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
影响因子:11.3
作者:Wu, Yang;Wang, Yichun;Yao, Hanhui;Li, Heng;Meng, Fanzheng;Li, Qidong;Lin, Xiansheng;Liu, Lianxin
通讯作者:Liu, Lianxin
DOI:10.1016/j.celrep.2022.111707
发表时间:2022-11
期刊:Cell reports
影响因子:8.8
作者:Qidong Li;H. Yao;Yichun Wang;Yang Wu;R. Thorne;Youming Zhu;Mian Wu;Lianxin Liu
通讯作者:Qidong Li;H. Yao;Yichun Wang;Yang Wu;R. Thorne;Youming Zhu;Mian Wu;Lianxin Liu
VCP乙酰化修饰导致肝癌免疫逃逸的机制研究
- 批准号:82373232
- 项目类别:面上项目
- 资助金额:48万元
- 批准年份:2023
- 负责人:刘连新
- 依托单位:
lncRNAHMMR-AS1/miR-188-3p/NCAPG2通路在肝细胞肝癌发生发展中的作用机制研究
- 批准号:81972307
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2019
- 负责人:刘连新
- 依托单位:
国内基金
海外基金
