CMaf-Inducing Protein Promotes LUAD Proliferation and Metastasis by Activating the MAPK/ERK Pathway.

Abstract

Objective Previous studies have shown that cMaf-inducing protein (CMIP) promotes tumorigenesis and progression, however, the role of CMIP in lung adenocarcinoma (LUAD) and its molecular mechanism remain unclear. Methods In this study, the Human Protein Atlas and Kaplan–Meier Plotter database were used to analyze the expression and prognostic value of CMIP in LUAD. Then, the expression levels of CMIP in LUAD tissues and cells were detected by qRT-PCR and western blot. The lentiviral vector was used to establish a stable transfected cell line, and the transfection efficiency was detected by qRT-PCR. MTT assay, colony formation assay, transwell assay, and wound healing assay were used to evaluate the function of CMIP in LUAD. In addition, the effect of CMIP on the MAPK/ERK pathway in LUAD cells was analyzed by western blot. Results The expression level of CMIP was significantly increased in LUAD cell and tissue samples, and the high expression of CMIP was associated with overall survival (OS) and progression-free survival (PFS) in LUAD patients. In vitro experiments showed that CMIP overexpression significantly promoted the proliferation, migration, and invasion of A549 cells. CMIP knockout significantly inhibited the proliferation, migration, and invasion of H1299 cells. In addition, it was observed that the expression levels of the MAPK/ERK pathway-related proteins were significantly increased in CMIP-overexpressed A549 cells, and promoted cell proliferation, migration, and invasion, while U0126 could significantly reverse the activation of the MAPK/ERK pathway by CMIP overexpression, and inhibit the proliferation, migration, and invasion of A549 cells. Conclusion Our study shows that CMIP, as an oncogene, is associated with poor patient prognosis, and may promote the proliferation and metastasis of LUAD by activating the MAPK/ERK pathway. Therefore, CMIP may be a new potential therapeutic target for LUAD.