CagA+ H.pylori促进lncRNA RCAN1表达在胃癌细胞侵袭转移中的作用及其分子机制研究

批准号:
81874196
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
谢霞
依托单位:
学科分类:
H1809.肿瘤复发与转移
结题年份:
2022
批准年份:
2018
项目状态:
已结题
项目参与者:
肖煜峰、李新哲、刘菁菁、杨敏、黄瑜、唐黎、高楠楠、胡家熙
国基评审专家1V1指导 中标率高出同行96.8%
结合最新热点,提供专业选题建议
深度指导申报书撰写,确保创新可行
指导项目中标800+,快速提高中标率
微信扫码咨询
中文摘要
Hp感染与胃癌侵袭转移密切相关,但机制尚不明确.我们前期通过lncRNA芯片筛选发现lncRNA RCAN1在CagA+Hp感染的胃癌细胞中高表达,与胃癌转移密切相关;FISH提示lncRNA RCAN1与其亲本基因RUNX1 pre-mRNA存在共定位,干扰lncRNA RCAN1可以降低RUNX1 pre-mRNA稳定性;通过生物信息学预测,RIP,qRT-PCR实验还发现lncRNA RCAN1可以与PTBP1蛋白结合,共同促进RUNX1 pre-mRNA的稳定性.根据文献和前期实验,我们提出"lncRNA RCAN1与CagA+Hp感染密切相关,通过结合PTBP1增强RUNX1 pre-mRNA稳定性,促进RUNX1表达,介导胃癌转移"的假说,并拟通过RNA pull-down,Co-IP,质谱分析,分子生物学,细胞生物学等加以证实,为胃癌术后根除Hp提供新的理论依据和作用靶点.
英文摘要
Hp infection is closely related with metastasis of gastric cancer, but the mechanism is not clear. Our previous experiment found that expression of lncRNA RCAN1 is high in CagA+Hp infected gastric cancer cells through the lncRNA chip, which is closely related to the metastasis of gastric cancer; FISH indicated that lncRNA RCAN1 and RUNX1 pre-mRNA, its parent gene, are colocalized, interference of lncRNA RCAN1 can reduce the stability of RUNX1 pre-mRNA; Bioinformatics analysis, RIP and qRT-PCR also show that lncRNA RCAN1 can bind with PTBP1 protein, and promote the stability of RUNX1 pre-mRNA jointly. According to the literature and previous experiment, we put forward the hypothesis: " lncRNA RCAN1 is closely related to CagA+Hp infection, it can combine with PTBP1 to enhance stability of RUNX1 pre-mRNA, promote the expression of RUNX1, accelerate metastasis of gastric cancer". This hypothesis will be confirmed by RNA pull-down, Co-IP, mass spectrometry analysis,molecular biology, cell biology experiment in the further study. The confirmation of this hypothesis will provide a new theoretical basis and target for the eradication of Hp after surgery of gastric cancer.
幽门螺杆菌(Helicobacter pylori,Hp)感染是已知最强的胃癌危险因素。在Hp感染期间,宿主细胞异常的表观遗传调控和表观遗传修饰可能是Hp感染诱导胃癌进展的重要原因,但机制尚不明确。课题组一方面通过lncRNA 芯片和细胞生物学实验阐明lncRNA TTC30B-1在CagA+Hp感染胃癌细胞中表达显著增高,且与胃癌患者不良预后密切相关;干扰和回复实验证实CagA+Hp上调lncRNA TTC30B-1促进细胞粘附信号通路是诱导胃癌细胞侵袭转移的关键机制。另一方面我们研究证实CagA+Hp感染显著降低胃癌细胞m6A水平,增强m6A去甲基化酶FTO的表达水平,进一步通过MeRIP-seq、MeRIP-PCR、RNA-seq等实验证实FTO以去甲基化酶依赖的方式诱导EMT相关基因表达,促进胃癌细胞发生EMT。因此,我们的研究揭示了CagA+Hp感染诱导胃癌细胞表观遗传调控异常,进而促进胃癌转移的分子机制,将为阻断及治疗Hp感染后胃癌进展提供新的靶点。
专著列表
科研奖励列表
会议论文列表
专利列表
长非编码RNA LINC00675稳定p53蛋白的分子机制及其在胃癌增殖中的作用研究
- 批准号:81502422
- 项目类别:青年科学基金项目
- 资助金额:18.0万元
- 批准年份:2015
- 负责人:谢霞
- 依托单位:
国内基金
海外基金
