肺腺癌易发生转移，肿瘤干细胞（CSCs）干性增加可能是其重要原因。申请人前期发现linc01290在肺腺癌中下调且与淋巴结转移，临床分期及预后呈负性相关。进一步发现上调linc01290可抑制CSCs干性且可通过IGF2BP1负性调控c-Myc、CD44稳定性介导该生物学效应。本项目拟开展如下研究来进一步阐明linc01290下调导致CSCs干性增强促转移机制：1确定linc01290负性调控CSCs干性参与转移的关键序列2确定IGF2BP1介导linc01290功能及关键结构域3明确linc01290通过IGF2BP1负性调控c-myc、CD44抑制干性4探索linc01290抑制IGF2BP1招募ELAVL1和/或与YTHDF2/3竞争m6A位点抑制干性5探索linc01290与IGF2BP1结合促进IGF2BP1泛素化降解。研究结果不仅能揭示肺腺癌转移机制，而且能为其治疗提供新靶点。

Lung adenocarcinoma is prone to metastasis, and the increased potential of cancer stem cells (CSCs) may be a critical reason. Our previous work found that lncRNA linc01290 was down-regulated in lung adenocarcinoma, and negatively correlated with lymph node metastasis, clinical stage, and prognosis. Further studies found that up-regulation of linc01290 could inhibit potentials of CSCs. Mechanism studies found that linc01290 could mediate these biological effects through negatively regulating c-myc and CD44 stability via directly binding to the KH3/4 domain of IGF2BP1. This proposal aims to further elucidate the molecular mechanism how linc01290 down-regulation leads to the increased potential of CSCs and metastasis of lung adenocarcinoma with the following methods: (1) to investigate the key region sequence of linc01290 that negatively regulates the potentials of cancer stem cells and metastasis of lung adenocarcinoma; (2) to investigate the key domain of IGF2BP1 that mediates linc01290 biological functions; (3) to investigate the specific mechanism of linc01290 that inhibits CSCs potentials by negatively regulating c-myc and CD44 through IGF2BP1; (4) to investigate whether linc01290 inhibits potentials of CSCs through inhibiting the recruitment of ELAVL1 by IGF2BP1 or m6A locus by competing with YTHDF2/3; and (5) to investigate linc01290 that promotes the ubiquitination degradation of IGF2BP1 via directly binding with it. The findings will not only reveal the metastasis mechanism of lung adenocarcinoma, but also provide a new target for its treatment.