circ_0001790/miR-509-3-5P/GINS4通路在胃癌生长中的作用及其机制
批准号:
81772526
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
黄陈
依托单位:
学科分类:
H1803.肿瘤细胞命运
结题年份:
2021
批准年份:
2017
项目状态:
已结题
项目参与者:
温玉刚、邓标、夏翔、朱中林、章靖、骆广涛、余志龙
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中文摘要
研究胃癌发生发展机制、寻找诊治和预后判断靶点是胃癌研究领域的热点。前期通过TCGA数据库发现GINS4在胃癌组织中表达高于癌旁组织;PCR结果示GINS4在正常胃粘膜、癌前病变、胃癌组织中表达逐渐增高;体外实验发现GINS4促进胃癌细胞生长。为阐明GINS4的调控机制,利用circRNA测序、miRNA芯片和生物信息学分析发现circ_0001790/miR-509-3-5P可能调控GINS4。鉴于此,推测circ_0001790通过海绵样作用吸附miR-509-3-5P,解除其对GINS4的抑制,从而促进胃癌进展。为验证此推测,分别调控三者表达,研究其对胃癌生长的影响;RIP等实验研究GINS4的上、下游调控分子;检测组织和血浆中三者表达与病理和预后的关系。旨在阐明circ_0001790/miR-509-3-5P/GINS4通路在胃癌生长中的作用和机制,发现新的胃癌诊治和预后判断靶点。
英文摘要
In the field of gastric cancer, studying the molecular mechanisms of carcinogenesis and progression of gastric cancer, and searching for diagnosis, treatment and prognosis judgment indicators are becoming the hot topics. In the early stage, it was found that GINS4 expression was obviously higher in gastric cancer than that in the adjacent normal tissue through TCGA data base. Additionally, PCR results indicated that GINS4 expression was gradually increased from normal gastric mucosa, precancerous lesion to gastric cancer tissue. Moreover, in vitro experiments revealed that the growth of gastric cancer cells was promoted by GINS4. To clarify the regulation mechanism of GINS4, we found that circ_0001790/miR-509-3-5P pathway may regulate GINS4 by employing the circRNA sequencing, miRNA microarray and bioinformatics assays. Based on the previous results, we put forward the assumption that circ_0001790 relieves the inhibited function of miR-509-3-5P on GINS4 via sponging miR-509-3-5P, and then promotes carcinogenesis and progression of gastric cancer. In order to verify this speculation, we will separately regulate their expression to study the effect of circ_0001790, miR-509-3-5P and GINS4 on the growth of gastric cancer. RIP and other assays will be applied to study upstream and downstream regulation mechanism of GINS4. The expression of circ_0001790, miR-509-3-5P and GINS4 and their relations with the pathology and prognosis of gastric cancer will be validated separately in tissue and plasma. The purpose of this study is to elucidate the effect and mechanism of circ_0001790/miR-509-3-5P/GINS4 pathway in the growth of gastric cancer, and to provide new molecular biomarkers for diagnosis, treatment and prognosis of gastric cancer.
在真核生物中,GINS复合体亚单位4(GINS4)在启动DNA复制和延长细胞周期G1/S期中发挥关键作用,但其功能和作用机制尚不清楚。本课题组前期研究发现,GINS4在胃癌组织中表达高于癌旁组织,其表达在正常胃粘膜、癌前病变、胃癌组织中表达逐渐增高,且体外实验发现GINS4能够促进胃癌细胞生长。进一步通过circRNA测序、miRNA芯片和生物信息学分析发现,circ_0001790/miR-509-3-5p可能对GINS4发挥调控作用。基于上述研究基础,本课题组通过联合TCGA数据库、Oncomine数据库及qRT-PCR、Western blotting方法检测GINS4的表达情况,进一步证实GINS4在胃癌组织和细胞中的高表达。结合病理分期等指标发现GINS4表达与肿瘤分化程度、T分期、N分期、疾病分期均呈正相关。K-M生存分析发现高GINS4患者总生存期(Overall survival,OS)和无病生存期(Disease-free survival, DFS)均低于低GINS4胃癌患者。通过上下调细胞中GINS4的表达发现其与生长增殖、细胞周期、细胞凋亡相关。进一步探究发现,GINS4能够直接结合和激活Rac1和CDC42,而circMLLT10(circ_0001790)能够通过结合miR-509-3-5p减弱其对靶标GINS4的抑制作用。同时,circMLLT10促进细胞生长与转移,抑制细胞凋亡,而miR-509-3-5p抑制细胞生长和转移,促进细胞凋亡。这一发现有望为胃癌的精准诊断和治疗提供新的潜在靶点。项目研究成果在Theranostics、Gastric Cancer等期刊发表论文5篇。
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
One stomach, two subtypes of carcinoma-the differences between distal and proximal gastric cancer.
一个胃,两种癌亚型——远端胃癌和近端胃癌的区别
DOI:10.1093/gastro/goab050
发表时间:2021-12
期刊:Gastroenterology report
影响因子:3.6
作者:Zhang Y;Zhang PS;Rong ZY;Huang C
通讯作者:Huang C
Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/vimentin axis
环状RNA circNHSL1通过miR-1306-3p/SIX1/波形蛋白轴促进胃癌进展
DOI:10.1186/s12943-019-1054-7
发表时间:2019-08
期刊:Molecular Cancer
影响因子:37.3
作者:Zhonglin Zhu;Zeyin Rong;Zai Luo;Zhilong Yu;Jing Zhang;Zhengjun Qiu;Chen Huang
通讯作者:Chen Huang
The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42
新型 GINS4 轴通过激活 Rac1 和 CDC42 促进胃癌生长和进展
DOI:10.7150/thno.36256
发表时间:2019-01-01
期刊:THERANOSTICS
影响因子:12.4
作者:Zhu, Zhonglin;Yu, Zhilong;Huang, Chen
通讯作者:Huang, Chen
MEF2A-mediated lncRNA HCP5 Inhibits Gastric Cancer Progression via MiR-106b-5p/p21 Axis.
MEF2A 介导的 lncRNA HCP5 通过 MiR-106b-5p/p21 轴抑制胃癌进展。
DOI:10.7150/ijbs.55020
发表时间:2021
期刊:International journal of biological sciences
影响因子:9.2
作者:Chen W;Zhang K;Yang Y;Guo Z;Wang X;Teng B;Zhao Q;Huang C;Qiu Z
通讯作者:Qiu Z
DOI:10.1016/j.bbcan.2021.188634
发表时间:2021
期刊:BBA - Reviews on Cancer
影响因子:--
作者:Yitian Xu;Pengshan Zhang;Kundong Zhang;Chen Huang
通讯作者:Chen Huang
缺氧诱导的circIREB2通过编码多肽IREB2-268aa促进胃癌EMT和转移的机制研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2020
- 负责人:黄陈
- 依托单位:
Caveolin-1在胰腺癌转移和EMT中的作用及其机制研究
- 批准号:81101844
- 项目类别:青年科学基金项目
- 资助金额:20.0万元
- 批准年份:2011
- 负责人:黄陈
- 依托单位:
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