Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway

Respiratory Research

Research

Ning Zhang¹  Zhouzhong Liu²  Xuwang Lai²  Yuli Wang²  Shubin Liu² 

[1] Department of Gastroenterology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang University, 341000, Ganzhou City, Jiangxi Province, China;Department of Oncology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang University, 341000, Ganzhou City, Jiangxi Province, China;

关键词: Lung adenocarcinoma;    CD147;    Transcriptome sequencing;    Lipid metabolism;    Rap1 signaling pathway;   

DOI  :  10.1186/s12931-023-02532-0

 received in 2023-03-10, accepted in 2023-09-05,  发布年份 2023

来源: Springer

【 摘 要 】

ObjectiveCD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms.MethodsFollowed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments.ResultsCD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results.ConclusionsSilencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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