转录因子Sp1活化FALEC靶向DNMT1促进上皮性卵巢癌侵袭转移的作用机制

Long non-coding RNAs (LncRNAs) have been pervasively transcribed in genome,which regulate gene expressions at multiple levels to involve in tumor metastasis.The applicant has found that LncRNA FALEC could bind to protein DNMT1, and knockdown its expression inhibited ovarian cancer cells metastasis and the expression of DNMT1.In addition, bioinformatics predicted that Sp1 bound with FALEC promoter.The purpose of this project is to investigate the mechanism by which Sp1 regulates FALEC to promote ovarian cancer cells metastasis, and to explore the mechanism by which FALEC binds with DNMT1 to induce cancer cells invasion and migration, and to elucidate the mechanism by which Sp1/FALEC/DNMT1 signaling pathway mediates cancer metastasis in epithelial ovarian cancer cells and in nude mice xenografted with ovarian cancer cells. We believe that achieving these goals will reveal a novel molecular mechanism of ovarian cancer cells metastasis, and provide new theoretical and experiments basis for developing novel anti-tumor target in epithelial ovarian cancer.

长链非编码RNAs(LncRNAs)在基因组中广泛存在并从多个层面调控基因表达进而介导肿瘤侵袭转移。申请者发现在上皮性卵巢癌细胞中FALEC能够结合蛋白DNMT1,敲除其表达可以抑制肿瘤细胞侵袭转移及DNMT1表达。此外,信息学预测转录因子Sp1与FALEC启动子区存在特异结合位点。本项目拟阐明Sp1调控FALEC介导卵巢癌细胞侵袭转移的机制,验证FALEC结合DNMT1促进肿瘤细胞侵袭转移,并在上皮性卵巢癌细胞和荷瘤鼠模型上证实Sp1/FALEC/DNMT1信号通路介导卵巢癌细胞侵袭转移的机制。本研究将为阐明上皮性卵巢癌侵袭转移作用的分子机制提供新思路,为开发有效抑制卵巢癌侵袭转移的新型靶基因提供理论与实验依据。

长链非编码RNAs(LncRNAs)在基因组中广泛存在并从多个层面调控基因表达进而介导肿瘤侵袭转移。本项目证实转录因子 Sp1 与 FALEC 启动子区结合，并转录水平调控其表达，进而 FALEC 靶向 DNMT1 通过调控下游效应因子介导上皮性卵巢癌侵袭转移的发生。本研究将为阐明上皮性卵巢癌侵袭转移作用的分子机制提供新思路,为开发有效抑制卵巢癌侵袭转移的新型靶基因提供理论与实验依据。