AAMP通过调节YAP信号通路促进骨肉瘤细胞转移的机制研究  

AAMP Promotes Osteosarcoma Cell Metastasis by Regulating YAP Signaling Pathway

作　　者：邓乾蓉 占方彪 谢朝政 向双 陈建 杨毅 DENG Qianrong;ZHAN Fangbiao;XIE Chaozheng;XIANG Shuang;CHEN Jian;YANG Yi(Postgraduate Training Base of Jinzhou Medical University,Chongqing University Three Gorges Hospital,Chongqing 404000,China;Health Management Center,Chongqing University Three Gorges Hospital,Chongqing 404000,China;Department of Orthopedics,Chongqing University Three Gorges Hospital,Chongqing 404000,China;Department of Gastrointestinal Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China;Department of Pathology,Chongqing University Three Gorges Hospital,Chongqing 404000,China;Department of Hematology,Chongqing University Three Gorges Hospital,Chongqing 404000,China)

机构地区：[1]锦州医科大学研究生培养基地,重庆大学附属三峡医院,重庆404000 [2]重庆大学附属三峡医院健康管理中心,重庆404000 [3]重庆大学附属三峡医院骨科,重庆404000 [4]重庆医科大学附属第一医院胃肠外科,重庆400016 [5]重庆大学附属三峡医院病理科,重庆404000 [6]重庆大学附属三峡医院血液科,重庆404000

出　　处：《肿瘤防治研究》2024年第6期440-447,共8页Cancer Research on Prevention and Treatment

基　　金：重庆市自然科学基金面上项目(cstc2021jcyjmsxmX0909);重庆市中青年医学高端人才项目(33158);重庆大学附属三峡医院青年人才重点项目(2022YJKYXM-043);重庆市万州区博士“直通车”科研项目(wzstc20230404)。

摘　　要：目的研究AAMP在骨肉瘤细胞中的作用,探索AAMP通过YAP信号通路调节骨肉瘤细胞侵袭转移的机制。方法利用公共测序数据分析AAMP与骨肉瘤的相关性,q-PCR、Western blot、免疫组织化学检测骨肉瘤细胞中相关分子表达水平,CCK-8检测细胞增殖能力,Trans-well、划痕实验检测骨肉瘤细胞的侵袭、转移能力,免疫荧光检测相关分子的细胞定位及表达。结果AAMP高表达与骨肉瘤患者预后负相关(P<0.05),AAMP在转移性骨肉瘤患者中表达水平升高(P<0.05)。与对照组相比,敲低AAMP后骨肉瘤细胞的迁移、侵袭和EMT活性明显下降(P<0.05)。敲低AAMP后p-CFL1表达水平减低,且细胞板状伪足明显减少(P<0.05)。AAMP和YAP在骨肉瘤细胞中表达呈正相关(P<0.05)。进一步验证了干扰YAP表达可以影响骨肉瘤细胞的迁移和侵袭能力。结论AAMP通过调节YAP信号通路促进骨肉瘤细胞转移,提示AAMP可能为促进骨肉瘤侵袭转移的关键分子。Objective To determine the role of AAMP in osteosarcoma cells and explore the mechanism of invasion and metastasis of osteosarcoma cells regulated by AAMP through the YAP signaling pathway.Methods Public sequencing data analysis was used to explore the correlation between AAMP and osteosarcoma.q-PCR,Western blot,and immunohistochemistry were used to detect the expression levels of osteosarcoma cell-related molecules.CCK-8 was used to detect cell proliferation ability.Transwell and wound healing assays were used to detect the invasive and metastatic abilities of osteosarcoma cells.Immunofluorescence was used to detect the cell localization and expression levels of related molecules.Results High expression of AAMP was negatively correlated with the prognosis of patients with osteosarcoma(P<0.05),and the expression of AAMP in patients with metastatic osteosarcoma increased(P<0.05).Compared with the control group,the AAMP interference group showed significantly decreased migratory,invasive,and EMT activities(P<0.05).The expression of p-CFL1 reduced after the knockdown of AAMP,and the cell plate pseudopods decreased significantly(P<0.05).A positive correlation was found between the expression levels of AAMP and YAP in osteosarcoma cells(P<0.05).Interfering with YAP expression can affect the migration and invasion of osteosarcoma cells.Conclusion AAMP promotes osteosarcoma cell metastasis by regulating the YAP signaling pathway,suggesting that AAMP may be a key molecule in promoting invasion and metastasis of osteosarcoma.

关 键 词：骨肉瘤 AAMP YAP 丝切蛋白1 转移 侵袭 伪足 

分 类 号：R73-37[医药卫生—肿瘤] R738[医药卫生—临床医学]