USP9X inhibits metastasis in pulmonary sarcomatoid carcinoma by regulating epithelial-mesenchymal transition, angiogenesis and immune infiltration

• Published in: Translational oncology 2024-09, Vol.47, p.101950, Article 101950
• Main Authors: Feng, Qin, Liu, Qian, Liu, Zi, Xu, Jianyu, Yang, Yang, Zhu, Ying, Lu, Guangxian, Xu, Guangjuan, Wu, Dan, Wang, Feng, Liu, Biao, Wang, Wenjuan, Ding, Xinyuan
• Format: Article
• Language: English
• Subjects: Angiogenesis; Epithelial-to-mesenchymal transition; Immune infiltration; Metastasis; Pulmonary sarcomatoid carcinomas; Ubiquitin-specific peptidase 9X
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2024.101950

•USP9X expression was negatively associated with metastasis in patients with PSC.•USP9X regulates EMT, angiogenesis and immunoinfiltration of PSC by inhibiting MMP9.•Targeting USP9X/MMP9 may be a promising strategy for inhibiting PSC metastasis. Pulmonary sarcomatoid carcinoma (PSC) is a highly invasive pulmonary malignancy with an extremely poor prognosis. The results of previous studies suggest that ubiquitin-specific peptidase 9X (USP9X) contributes to the progression of numerous types of cancer. Nevertheless, there is little knowledge about the molecular mechanisms and functions of USP9X in the metastasis of PSC. Immunohistochemistry and western blotting were used to detect USP9X expression levels in PSC tissues and cells. Wound healing, transwell, enzyme-linked immunosorbent assay (ELISA), tube formation, and aortic ring assays were used to examine the function and mechanism of USP9X in the metastasis of PSC. Expression of USP9X was markedly decreased and significantly correlated with metastasis and prognosis of patients with PSC. Then we revealed that USP9X protein levels were negatively associated with the levels of epithelial-mesenchymal transition (EMT) markers and the migration of PSC cells. It was confirmed that USP9X in PSC cells reduced VEGF secretion and inhibited tubule formation of human umbilical vein endothelial cells (HUVEC) in vitro. USP9X was detected to downregulate MMP9. Meanwhile, MMP9 was positively related to EMT, angiogenesis and was negatively related to immune infiltration in the public databases. USP9X was significantly negatively associated with the expression of MMP9, EMT markers, CD31, and positively associated with CD4, and CD8 in PSC tissues. The present study reveals the vital role of USP9X in regulating EMT, angiogenesis and immune infiltration and inhibiting metastasis of PSC via downregulating MMP9, which provides a new effective therapeutic target for PSC.