Abstract
Lung adenocarcinoma (LUAD) is the most metastatic, invasive, and fatal tumor type of non-small cell lung cancer that lacks satisfying therapy. The purpose of this work is to investigate the effects of proteasome 26S subunit, non-ATPase 1 (PSMD1) on the progression of LUAD. Specific PSMD1 short hairpin RNA and PSMD1-overpression vectors were used to modify the expression of PSMD1 in LUAD cell lines. A xenograft model of LUAD was established with 5 × 106 stable PSMD1-downregulated A549 cells. The results showed that PSMD1 silence repressed the cell proliferation and induced the cell cycle arrest as well as the apoptosis of A549 and HCC827 cells. While the upregulation of PSMD1 led to the opposite. Furthermore, the results of co-immunoprecipitation revealed that PSMD1 interacted with PTEN-induced kinase 1 (PINK1). And PSMD1 inhibited the ubiquitination and enhanced the stability of PINK1 protein. Subsequently, we found that PSMD1 promoted the viability and repressed the apoptosis of LUAD cells by stabilizing PINK1. PSMD1 knockdown suppressed the malignant phenotypes of LUAD in ex vivo experiments, as well as the in vivo growth of LUAD tumor by the degradation of PINK1. In summary, PSMD1 facilitated the progression of LUAD by the regulation of PINK1.
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