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LAMC2 regulates proliferation, migration, and invasion mediated by the Pl3K/AKT/mTOR pathway in oral

查看全文 作　　者：FAYU [1]SHAN;LANLAN [1]LIANG;CHONG [1]FENG;HONGBAO [1]XU;ZIROU [1]WANG;WEILI [1]LIU;LINGLING [1]PU;ZHAOLI [1]CHEN;GANG [2]CHEN;XINXING [1]WANG 高影响力作者 机构地区：[1]Department of Environmental Medicine,Tianjin Institute of Environmental and Operational Medicine,Tianjin,300070,China;[2]School and Hospital of Stomatology,Tianjin Medical University,Tianjin,300050,China高影响力机构 出　　处：《Oncology Research》索引2023年第31卷第4期,共13页高影响力期刊 基　　金：This work was supported by the National Natural Science Foundation of China(Grant Numbers 31971106,BWS21L013,21WS09002,JK20211A010213). 摘　　要：Background:Oral squamous cell carcinoma(OSCC)is a common malignant tumor.Recently,Laminin Gamma 2(LAMC2)has been shown to be abnormally expressed in OSCC;however,how LAMC2 signaling contributes to the occurrence and development of OSCC and the role of autophagy in OSCC has not been fully explored.This study aimed to analyze the role and mechanism of LAMC2 signaling in OSCC and the involvement of autophagy in OSCC.Methods:To explore the mechanism by which LAMC2 is highly expressed in OSCC,we used small interfering RNA(siRNA)to knock down LAMC2 to further observe the changes in the signaling pathway.Furthermore,we used cell proliferation assays,Transwell invasion assays,and wound-healing assays to observe the changes in OSCC proliferation,invasion,and metastasis.RFP-LC3 was used to detect the level of autophagy intensity.A cell line-derived xenograft(CDX)model was used to detect the effect of LAMC2 on tumor growth in vivo.Results:This study found that the level of autophagy was correlated with the biological behavior of OSCC.The downregulation of LAMC2 activated autophagy and inhibited OSCC proliferation,invasion,and metastasis via inhibiting the PI3K/AKT/mTOR pathway.Moreover,autophagy has a dual effect on OSCC,and the synergistic downregulation of LAMC2 and autophagy can inhibit OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.Conclusions:LAMC2 interacts with autophagy to regulate OSCC metastasis,invasion,and proliferation via the PI3K/AKT/mTOR pathway.LAMC2 down-regulation can synergistically modulate autophagy to inhibit OSCC migration,invasion,and proliferation. 关 键 词：LAMC2 OSCC AUTOPHAGY PI3K/AKT/mTOR pathway 3-Methyladenine RAPAMYCIN
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