课题基金基金详情
lncRNA ILF3DT通过hnRNPM调控CD44可变剪切抑制卵巢癌侵袭转移的机制研究
结题报告
批准号:
82002747
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
吴勇
依托单位:
学科分类:
肿瘤表观遗传
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
吴勇
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中文摘要
卵巢癌是致死率最高的妇科恶性肿瘤之一,其发病隐匿,发现时多为晚期,且复发率极高,故揭示其转移复发机制并探寻新的治疗靶点是研究的重点也是难点。本项目前期通过高通量筛选正常卵巢组织和卵巢癌组织中差异表达的基因,发现lncRNA ILF3DT可能是潜在的卵巢癌抑癌基因,可以抑制卵巢癌细胞的增殖以及侵袭转移。并且研究发现在卵巢癌中,ILF3DT可能参与调控hnRNPM对CD44基因的可变剪切,但目前其具体调控功能以及作用机理仍不明确。据此,本课题假设ILF3DT是卵巢癌的抑癌基因,拟在前期工作基础上利用一系列的体内外实验来探讨ILF3DT-hnRNPM-CD44调控轴在卵巢癌中的内在功能网络及其促进肿瘤转移复发的作用机制,并明确其中关键分子与卵巢癌临床病理及预后的相关性,这对于更好地明确卵巢癌转移复发机制、完善卵巢癌转移复发风险评估模型和寻找卵巢癌治疗的新靶点具有重要的理论意义和潜在临床转化价值
英文摘要
Ovarian cancer is one of the gynecological malignancies with the highest mortality. Because of its latent onset and high recurrence rate,patients with ovarian cancer are usually found to be metastatic or recurrent. So revealing metastatic mechanism and exploring new therapeutic targets have become one of the key problems that are urgent to be resolved in ovarian cancer study. However, it is also very difficult. Through high throughput screening of genes differentially expressed in normal ovarian tissue and tumor tissues, we found that long noncoding RNA ILF3DT was a potential tumor suppressor gene in ovarian cancer, which can inhibit the proliferation, invasion and metastasis of ovarian cancer cells. Subsequently, we found that ILF3DT may regulate the alternative splicing of CD44 by binding hnRNPM in ovarian cancer, but the specific regulatory function and mechanism of this signaling pathway are still unclear at present. Therefore, we hypothesize that ILF3DT is a suppressor gene of ovarian cancer, and we have done a lot of preliminary experiments. Based on our previous experiment results, we will further use in vivo and in vitro experiments to explore the underlying intrinsic regulatory mechanism of ILF3DT-hnRNPM-CD44 axis in ovarian cancer and its role in promoting metastasis and recurrence of ovarian cancer. Besides, we will clarify the correlation between these key molecules and clinicopathologic factors and prognosis of ovarian cancer in this study. Therefore, our study will be of great theoretical significance and potential clinical value for better understanding the metastatic and recurrent mechanisms of ovarian cancer, improving the risk assessment model of metastasis and recurrence for ovarian cancer, and identifying critical molecular targets for ovarian cancer treatment.
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DOI:10.1186/s13048-022-00969-3
发表时间:2022-03-31
期刊:Journal of ovarian research
影响因子:4
作者:Chen S;Wu Y;Wang S;Wu J;Wu X;Zheng Z
通讯作者:Zheng Z
DOI:10.1002/advs.202304638
发表时间:2023-11
期刊:ADVANCED SCIENCE
影响因子:15.1
作者:Wu, Yong;Chen, Siyu;Shao, Yang;Su, Ying;Li, Qin;Wu, Jiangchun;Zhu, Jun;Wen, Hao;Huang, Yan;Zheng, Zhong;Chen, Xiaojun;Ju, Xingzhu;Huang, Shenglin;Wu, Xiaohua;Hu, Zhixiang
通讯作者:Hu, Zhixiang
HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway.
HNRNPH1 稳定的 LINC00662 通过激活 GRP78/p38 通路促进卵巢癌进展。
DOI:10.1038/s41388-021-01884-5
发表时间:2021-07
期刊:Oncogene
影响因子:8
作者:Wu Y;Guo Q;Ju X;Hu Z;Xia L;Deng Y;Zhao P;Zhang M;Shao Y;Huang S;He X;Wen H;Wu X
通讯作者:Wu X
DOI:10.1186/s12967-022-03245-6
发表时间:2022-01-21
期刊:Journal of translational medicine
影响因子:7.4
作者:Wu J;Wu Y;Guo Q;Wang S;Wu X
通讯作者:Wu X
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