SPAG1 Inhibits Cell Proliferation and Tumor Growth of Lung Adenocarcinoma via the AKT/mTORC1 Signaling Axis

Abstract Background Sperm-associated antigen 1 (SAPG1) expression is increased in multiple cancer tissues, but the role and mechanisms of SPAG1 in lung cancer remain unknown. The present study was aimed to investigate SPAG1’s function and mechanisms in lung adenocarcinoma (LUAD). MethodsSPAG1 expression in LUAD tissues was evaluated by analyzing three LUAD datasets, and its association with prognosis of patients with LUAD was accessed by using Kaplan-Meier Plotter. The role of SPAG1 and its mechanisms were investigated in LUAD cells in vitro. The effect of SPAG1 on tumor growth was evaluated in LUAD tumor xenografts. In addition, the molecular domain involved in the regulation of cell proliferation was mapped. ResultsThe bioinformatical results showed that SPAG1 expression was increased significantly in LUAD tissues compared with normal lung tissues, and its high expression was associated with favorable prognosis, including overall survival (OS), first progression (FP) and post-progression survival (PPS). The results of in vitro experiments showed that SPAG1 suppressed cell proliferation, but enhanced autophagy via inhibiting AKT/mechanistic target of rapamycin (mTOR) complex 1 signaling axis, and that the region of 130~170 amino acid residues in SPAG1 is involved in the regulation of AKT and cell proliferation. The results of tumor xenografts demonstrated that SPAG1 knockdown promotes LUAD tumor growth and enhances AKT/mTORC1 signaling. ConclusionSPAG1 is upregulated in LUAD tissues and associated with favorable prognosis of patients with LUAD, and plays an inhibitory role in cell proliferation and tumor growth of LUAD through the AKT/mTORC1 signaling axis.