沉默 CD147 通过阻断 Rap1 信号通路抑制肺腺癌细胞增殖、迁移、侵袭、脂质代谢失调并促进细胞凋亡。
Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway.
机构信息
Department of Gastroenterology, Ganzhou People's Hospital, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou City, 341000, Jiangxi Province, China.
Department of Oncology, Ganzhou People's Hospital, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou City, 341000, Jiangxi Province, China.
出版信息
Respir Res. 2023 Oct 25;24(1):253. doi: 10.1186/s12931-023-02532-0.
OBJECTIVE
CD147 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.
METHODS
Followed 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.
RESULTS
CD147 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.
CONCLUSIONS
Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.
目的
CD147 是一种重要的糖蛋白，参与多种癌症的进展。本研究旨在探讨 CD147 在肺腺癌（LUAD）中的具体功能，并揭示相关的下游分子机制。
方法
沉默 CD147 后，通过 CCK8、划痕愈合、Transwell 检测和流式细胞术分别检测 LUAD 细胞的活力、迁移、侵袭和凋亡。通过 qRT-PCR 检测 CD147 和两种脂质代谢标志物（FASN 和 ACOX1）的表达。构建异种移植肿瘤模型，研究 CD147 在体内的功能。然后进行转录组测序，以探讨潜在的机制。通过 Western blot 检测 Rap1 和 p-p38 MAPK/p38 MAPK 的表达，通过免疫组化检测 CD147 和脂质代谢标志物（FASN、ACOX1）的变化。此外，应用 Rap1 激活剂和 Rap1 抑制剂进行反馈功能实验。
结果
CD147 在 LUAD 细胞中上调，沉默 CD147 抑制细胞增殖、迁移、侵袭、脂质代谢失调并促进凋亡，而过表达 CD147 则表现出相反的结果。沉默 CD147 还抑制了小鼠肿瘤异种移植的生长。转录组测序显示 834 个上调的差异表达基因（DEGs）和 602 个下调的 DEGs。经过功能富集，选择 Rap1 信号通路作为潜在靶点，然后验证其被 CD147 沉默阻断。此外，Rap1 激活剂的处理削弱了 si-CD147 对 LUAD 细胞增殖、迁移、侵袭和脂质代谢的抑制作用，而 RAP1 抑制剂的干预则表现出相反的结果。
结论
沉默 CD147 通过阻断 Rap1 信号通路抑制 LUAD 细胞的增殖、迁移、侵袭、脂质代谢失调和促进凋亡。
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