Department of Pulmonary Medicine, Shanghai Jinshan Tinglin Hospital, Shanghai, P.R. China.
Department of Pulmonary and Critical Care Medicine, 66324Shanghai East Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231161139. doi: 10.1177/15330338231161139.
This study aims to investigate the function of the protein arginine methyltransferase 5 (PRMT5) and fibroblast growth factor receptor 3 (FGFR3)/Akt signaling axis in the epithelial-mesenchymal transition (EMT) of human lung cancer. The mRNA and protein expression levels of PRMT5, FGFR3, p-Akt, and EMT markers are determined by quantitative real-time PCR and Western blotting, respectively; the expression and localization of PRMT5, p-Akt, and proliferating cell nuclear antigen are detected by immunofluorescence; the human lung cancer cell proliferation is measured by MTS assay. PRMT5 and FGFR3 are highly expressed in human lung cancer tissues and are closely related to lymphatic metastasis. Moreover, down-regulation of PRMT5 by lentivirus-mediated shRNAs or inhibition of PRMT5 by specific inhibitors attenuates FGFR3 expression, Akt phosphorylation, and lung cancer cell proliferation. Further studies show that silencing PRMT5 impairs EMT-related markers, including vimentin, collagen I, and β-catenin. Conversely, ectopic expression of PRMT5 increases FGFR3 expression, Akt phosphorylation, and EMT-related markers, suggesting that PRMT5 regulates metastasis probably through the FGFR3/Akt signaling axis. PRMT5/FGFR3/Akt signaling axis controls human lung cancer progression and metastasis and also implies that PRMT5 may serve as a prognostic biomarker and therapeutic candidate for treating lung cancer.
本研究旨在探讨蛋白质精氨酸甲基转移酶 5（PRMT5）和纤维母细胞生长因子受体 3（FGFR3）/Akt 信号轴在人肺癌上皮-间充质转化（EMT）中的作用。通过定量实时 PCR 和 Western blot 分别测定 PRMT5、FGFR3、p-Akt 和 EMT 标志物的 mRNA 和蛋白表达水平；通过免疫荧光检测 PRMT5、p-Akt 和增殖细胞核抗原的表达和定位；通过 MTS 测定人肺癌细胞的增殖。PRMT5 和 FGFR3 在人肺癌组织中高表达，与淋巴转移密切相关。此外，通过慢病毒介导的 shRNAs 下调 PRMT5 或特异性抑制剂抑制 PRMT5，可减弱 FGFR3 表达、Akt 磷酸化和肺癌细胞增殖。进一步研究表明，沉默 PRMT5 可损害 EMT 相关标志物，包括波形蛋白、胶原 I 和 β-连环蛋白。相反，PRMT5 的异位表达增加 FGFR3 表达、Akt 磷酸化和 EMT 相关标志物，表明 PRMT5 通过 FGFR3/Akt 信号轴调节转移。PRMT5/FGFR3/Akt 信号轴控制人肺癌的进展和转移，也暗示 PRMT5 可能作为治疗肺癌的预后生物标志物和治疗候选物。
