miR-205及其宿主基因MIR205HG协同促进鼻咽癌侵袭转移的机制研究

Distant metastasis is the main reason for the failure of NPC treatment. Based on transcriptome sequencing, we obtained a function unknowned LncRNA: MIR205HG with high expression in metastatic tissues. Our preliminary studies suggested that MIR205HG was a LncRNA of the host gene of miR-205,MIR205HG / miR-205 co-expression was correlated with N stage and poor prognosis; Silencing MIR205HG / miR-205 respectively, inhibited cell invasion and migration; miR-205 is targeted to EPB41L1 that could inhibit metastasis, while MIR205HG binds to ELAV1 protein and then up-regulates the transfer gene EPB41L5. Therefore, the scientific hypothesis that "MIR205HG / miR-205 binds ELAVl to up-regulate EPB41L5 and bind EPB41L1 synergistically to promote invasion and metastasis of nasopharyngeal carcinoma" was proposed. The project aims to demonstrate the synergistic effect of MIR205HG / miR-205 in invasion and metastasis of nasopharyngeal carcinoma in vitro and in vivo. The rescue experiment, RIP, pull-down and so on elucidated the molecular mechanism of MIR205HG / miR-205 cooperating to promote invasion and metastasis by targeting EPB41L1 and EPB41L5. This study will provide a new target for the prevention and treatment of nasopharyngeal carcinoma.

远处转移是鼻咽癌治疗失败主要原因，通过转录组测序我们发现miR205和功能未知的宿主基因LncRNA MIR205HG高表达于转移组织。前期发现：miR-205与宿主基因MIR205HG共转录表达上调，与N分期和不良预后相关；共沉默MIR205HG/miR-205，协同抑制细胞侵袭迁移；miR-205靶向结合抑转移基因EPB41L1，而MIR205HG绑定ELAV1蛋白上调促转移基因EPB41L5。故提出“MIR205HG/miR-205分别通过绑定ELAV1上调EPB41L5、结合EPB41L1，协同促进鼻咽癌侵袭转移”的科学假说。项目拟体内外证实MIR205HG/miR-205协同促进鼻咽癌侵袭转移；挽救实验、RIP、pull-down等阐述MIR205HG/miR-205通过靶向EPB41L1和EPB41L5协同促进侵袭转移的分子机制。本研究将为鼻咽癌的防治提供新靶标。

远处转移是鼻咽癌治疗失败主要原因，通过转录组测序我们发现miR-205和功能未知的宿主基因LncRNA MIR205HG高表达于转移组织。miR-205与宿主基因MIR205HG共转录表达上调，与N分期和不良预后相关；MIR205HG和miR-205在体内外协同促进鼻咽癌侵袭迁移；Sp1促进MIR205HG和miR-205的转录激活；miR-205靶向结合抑转移基因TRAK2和RECK，而MIR205HG通过绑定TIMP3蛋白促进HERC2对其泛素化降解而上调促转移基因MMP2和MMP9。本研究将为鼻咽癌的防治提供新靶标。