超级增强子介导lncRNA-PCSE1促进前列腺癌转移的机制研究

Metastasis is an important cause of prostate cancer death. Previous studies have shown that lncRNA plays an important role in prostate cancer metastasis, but its molecular mechanism of regulation has not been elucidated. We preliminarily found that lncRNA-PCSE1 associated super enhancer promoted high expression of lncRNA-PCSE1 in prostate cancer cells, activated PI3K/Akt pathway and promoted invasion and metastasis of prostate cancer. Therefore, we propose a key mechanism of prostate cancer metastasis: super-enhancer mediates expression of lncRNA-PCSE1, activates PI3K/Akt signaling pathway, and promotes invasion and metastasis of prostate cancer. This study intends to further use the in vitro and in vivo experiments, co-immunoprecipitation and high-throughput sequencing techniques to elucidate the molecular mechanism of super-enhancer-mediated lncRNA-PCSE1 promotes metastasis of prostate cancer cells, and provide a theory for super-enhancer as a new target for prostate cancer treatment. basis.

转移是前列腺癌死亡的重要原因，既往研究表明lncRNA在前列腺癌转移中起重要作用，但其调控分子机制并未阐明。我们预实验发现前列腺癌细胞存在lncRNA-PCSE1相关超级增强子，促进lncRNA-PCSE1高表达，激活PI3K/Akt通路，促进前列腺癌侵袭转移。因此，我们提出前列腺癌转移关键机制:超级增强子调控lncRNA-PCSE1，激活PI3K/Akt信号通路，促进前列腺癌侵袭转移转移。本研究拟进一步采用体内外实验，免疫共沉淀和高通量测序等技术，阐明超级增强子介导lncRNA-PCSE1促进前列腺癌转移的分子机制，为超级增强子作为前列腺癌治疗新靶点提供理论基础。

转移是前列腺癌死亡的重要原因，在前列腺癌转移中起到关键作用。通过既往研究表明lncRNA在前列腺癌转移中起重要作用，但其调控分子机制并未阐明。我们通过临床病例分析，筛选鉴定lncRNA-PCSE1在前列腺癌组织及正常前列腺腺上皮组织中差异表达。进一步通过扩大样本量进行验证lncRNA-PCSE1表达。进一步对前列腺癌细胞进行H3K27ac丰度的免疫共沉淀-高通量测序(ChIP-seq)查找潜在前列腺癌相关超级增强子，对照超级增强子ChIP-Seq数据并与测序结果取交集，鉴定出lncRNA-PCSE1相关超级增强子；进一步通过细胞实验，证实超级增强子调控lncRNA-PCSE1可促进前列腺癌细胞侵袭及转移能力；同时还构建骨转移动物模型，进一步说明其在骨转移中的作用。阐明超级增强子特异性调控 lncRNA-PCSE1表达，激活 PI3K/Akt 通路，促进前列腺癌转移的分子机制;为超级增强子作为前列腺癌治疗新靶点提供更充分的理论依据，以进一步指导临床实践。