RNA甲基化m5C介导TRNA-Glu剪切产生tRF-GM抑制肺腺癌侵袭转移的分子机制研究
结题报告
批准号:
82003106
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
夏文杰
依托单位:
学科分类:
肿瘤复发与转移
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
夏文杰
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中文摘要
tRNA衍生片段(tsRNA)与肿瘤的恶性进展密切相关。tRF-GM是申请人从m5C修饰水平变化的角度出发,筛选出的一条低表达于肺腺癌的tsRNA。前期实验显示tRF-GM受到肺腺癌细胞去m5C修饰调控;表达越低预后越差;体外实验表明过表达tRF-GM可抑制肺腺癌细胞侵袭转移。生物信息学预测及预实验显示tRF-GM可靶向结合E2F1,负向调节其表达。基于上述证据,本项目提出“去m5C修饰介导tRNA-Glu剪切产生tRF-GM可通过调节E2F1抑制肺腺癌侵袭转移”的科学假说。本研究拟采用RNA-BisSeq及BSP实验,证实甲基化转移酶NSUN2可作用于tRNA-Glu的特异性甲基化位点;同时开展体内实验、RIP及交叉拯救等实验阐明m5C甲基化/tRF-GM/E2F1轴调控肺腺癌侵袭转移的分子机制。m5C修饰调控tsRNA表达,从而介入肺腺癌的发展为全新视角,本研究可为肺癌防治提供新思路。
英文摘要
tsRNA (tRNA-derived small RNAs) plays an important role in tumor progression. By analyzing our previous tsRNA sequence data, we identified tRF-GM as a low expressed novel tsRNA (tRNA-derived small RNAs) in human lung adenocarcinoma. The expression level of tRF-GM is negatively correlated with the lymph node metastasis and positively correlate with the long-term survival time of patients significantly. In vitro experiment indicated that over-expression of tRF-GM repressed the invasion and metastasis of lung adenocarcinoma cell lines. Bioinformatic analysis and luciferase reporter gene assay experiment revealed that tRF-GM could target E2F1, a known oncogene, and promote its mRNA degradation. Based on the above clinical and experimental data, we hypothesized that “m5C demethylation mediated generation of tRF-GM could target E2F1 and thus inhibit he invasion and metastasis of lung adenocarcinoma”. For the current project aims, first we plan to apply RNA-BisSeq and BSP to validate that tRNA methyhransferases NSUN2 could act on the specific methylation site of tRNA-Glu and facilitate the generation of tRF-GM. Secondly, the mechanism of m5C methylation/tRF-GM/E2F1 axis to regulate the metastasis in lung adenocarcinoma will be deeply validated by RNA pull down, RIP and rescue experiments. This project may provide the new way for the prevention and treatment of lung adenocarcinoma.
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DOI:10.3390/cancers16010077
发表时间:2023-12-22
期刊:CANCERS
影响因子:5.2
作者:Shi, Yuanjian;Feng, Yipeng;Wang, Qinglin;Dong, Gaochao;Xia, Wenjie;Jiang, Feng;Mirshahi, Massoud
通讯作者:Mirshahi, Massoud
DOI:10.1186/s13045-022-01331-2
发表时间:2022-08-18
期刊:JOURNAL OF HEMATOLOGY & ONCOLOGY
影响因子:28.5
作者:Zhang, Te;Xia, Wenjie;Song, Xuming;Mao, Qixing;Huang, Xing;Chen, Bing;Liang, Yingkuan;Wang, Hui;Chen, Yuzhong;Yu, Xinnian;Zhang, Zeyu;Yang, Wenmin;Xu, Lin;Dong, Gaochao;Jiang, Feng
通讯作者:Jiang, Feng
国内基金
海外基金