miR-483-5p调控ALCAM基因对肺癌转移的影响及机制研究

miR-483-5p is deregulated in a variety of cancers, and is closely related with the cancer prognosis. However, the roles and mechanisms of miR-483-5p in tumorigensis and progression are unclear. Our previous results revealed for the first time that there is a causal relationship between miR-483-5p expression and cancer metastasis in human lung cancer tissues. Furthermore, overexpression of miR-483-5p reduced the expression of the activated leukocyte cell adhesion molecule (ALCAM) and promoted lung cancer cell epithelial-to-mesenchymal transition (EMT), a key process of metastasis，indicating the critical role of miR-483-5p in EMT and lung cancer invastion and metastasis by inhibiting ALCAM. Using lung cancer cell lines, animal models and clinical specimens, this project aims to investigate the roles and the mechanisms of miR-483-5p in lung cancer cell EMT and metastasis.The role of ALCAM and other possible targets in mediating lung cancer metastasis potential of miR-483-5p will be identified. Moreover, the regulation miR-483-5p by upstream singals and its mechanism will also be explored. This study will provide a novel mechanism for lung cancer metastasis, and identify miR-483-5p as a new marker for lung cancer metastasis and potential target for prevention and treatment of lung caner.

miR-483-5p在多种肿瘤中异常表达，并与预后密切相关，但其在肿瘤发生与进展中的作用与机制尚未阐明。课题组前期研究首次证实miR-483-5p在人肺癌组织中高表达，并与肺癌转移呈正相关。此外，miR-483-5p能抑制活化白细胞黏附分子(ALCAM)表达并促进肺癌细胞发生上皮-间质转变（EMT），提示miR-483-5p可能通过抑制ALCAM基因表达促进肺癌转移。本课题将利用肺癌细胞、动物的肿瘤转移模型和临床标本，从细胞到整体水平进一步研究miR-483-5p在肺癌转移中的作用，并探讨其分子机制；初步明确ALCAM及其他潜在的miR-483-5p靶分子在介导miR-483-5p促进肺癌转移中的作用，同时探索调节miR-483-5p表达的上游信号分子及其调节机制。本研究将为肺癌转移的病理发生机制与miR-483-5p的功能提供新内容，为miR-483-5p作为肺癌转移的标志物提供证据。

课题组前期研究首次证实miR-483-5p在人肺癌组织中高表达，并与肺癌转移呈正相关。此外，miR-483-5p能抑制活化白细胞黏附分子(ALCAM)表达并促进肺癌细胞发生上皮-间质转变（EMT），提示miR-483-5p可能通过抑制ALCAM基因表达促进肺癌转移。本课题利用肺癌细胞、动物的肿瘤转移模型和临床标本，从细胞到整体水平进一步表明miR-483-5p在肺癌中是一个促癌因子；并明确ALCAM在介导miR-483-5p促进肺癌转移中起着关键作用。同时，课题组还针对miR-661在肺癌中的作用展开了研究，研究发现miR-661在肺癌组织中是高表达的，和预后成显著的负相关；进一步研究表明miR-661促进肺癌细胞的增殖、迁移和转移，并明确RB1在介导miR-661促进肺癌转移中起着关键作用。。本研究将为肺癌转移的病理发生机制与miR-483-5p及miR-661的功能提供新内容，为miR-483-5p和miR-661作为肺癌转移的标志物提供证据。