LTR逆转座子来源的微肽PRMH1在同源重组修复中的作用及机制研究
结题报告
批准号:
32000892
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
许文丽
依托单位:
学科分类:
蛋白质、多肽与酶生物化学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
许文丽
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中文摘要
长非编码RNA(lncRNA)翻译生成的微肽是一类新的基因调控分子。前期我们已有研究报道,lncRNA编码的微肽KRASIM在肝癌中起着重要的抑癌功能。然而,这些隐蔽的微肽是否参与p53介导的同源重组(HR)修复通路并在肝癌发生发展中发挥重要的生物学作用尚不清楚。我们在近期的预实验中鉴定了一个LTR逆转座子来源的lncRNA编码的新功能微肽,其受到p53的负调控,可促进肝癌细胞HR修复,故命名为PRMH1。由此,我们推测,LTR逆转座子来源的微肽PRMH1是p53-HR修复通路的重要新成员,并在肝癌的发生发展中发挥重要的调控作用。本项目将在此基础上,通过系列实验,解析微肽PRMH1表达调控的分子机制,阐明微肽PRMH1在HR修复等生物学过程及肝癌发生发展中的作用及机制。本研究将揭示lncRNA编码的微肽在p53调控的HR修复通路中的重要作用,为肝癌的诊断与治疗提供新的标志物和靶点。
英文摘要
Micropeptides encoded by long non-coding RNAs (lncRNAs) are a novel class of gene regulators. Our previous study demonstrated that the lncRNA encoded micropeptide KRASIM played an important role in anticancer of hepatocellular carcinoma (HCC). However, whether these hidden micropeptides participate in the p53-regulated homologous recombination (HR) repair pathway and play a significant biological role in the occurrence and development of HCC is still unclear. Our preliminary experiments characterized that LTR retrotransposon-derived lncRNA encodes a novel functional micropeptide, called PRMH1, which is negatively regulated by p53 and can promote HR repair in HCC cells. Therefore, we hypothesize that the LTR-derived micropeptide PRMH1 is an important new member of the p53-regulated HR repair pathway and play a critical role in the occurrence and development of HCC. Based on the above findings, this project will employ a series of experiments to further decipher the molecular mechanism of the expressional regulation of the micropeptide PRMH1 and elucidate the role and mechanism of the micropeptide PRMH1 in the biological processes such as HR repair and the occurrence and development of HCC. Thus, this study will reveal the important roles of lncRNA-encoded micropeptides in p53-regulated HR repair pathway, and provide new biomarkers and targets for the diagnosis and treatment of HCC.
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专利列表
DOI:10.14218/jcth.2023.00224
发表时间:2024-01-28
期刊:Journal of clinical and translational hepatology
影响因子:3.6
作者:
通讯作者:
TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation.
TP53诱导的假定长非编码RNA编码抑制细胞增殖的功能性多肽
DOI:10.1101/gr.275831.121
发表时间:2022-06
期刊:GENOME RESEARCH
影响因子:7
作者:Xu, Wenli;Liu, Chang;Deng, Bing;Lin, Penghui;Sun, Zhenghua;Liu, Anrui;Xuan, Jiajia;Li, Yuying;Zhou, Keren;Zhang, Xiaoqin;Huang, Qiaojuan;Zhou, Hui;He, Qingyu;Li, Bin;Qu, Lianghu;Yang, Jianhua
通讯作者:Yang, Jianhua
DOI:10.1096/fj.202301019rr
发表时间:2023-11
期刊:The FASEB Journal
影响因子:--
作者:Jing Deng;Wenli Xu;Y. Jie;Yutian Chong
通讯作者:Jing Deng;Wenli Xu;Y. Jie;Yutian Chong
DOI:10.3389/fcimb.2022.923300
发表时间:2022
期刊:Frontiers in cellular and infection microbiology
影响因子:5.7
作者:
通讯作者:
国内基金
海外基金