Low expression of PRTN3 regulates the progression of gastric cancer by inhibition of cell cycle and promotion of apoptosis.

Abstract

Background: Proteinase 3 (PRTN3) has been linked to the progression of different cancer types. In this study, the expression and cell biological function of PRTN3 were investigated in gastric cancer (GC) to assess its role in GC progression.

Methods: The PRTN3 levels in 20 pairs of GC tissues were detected via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting, while immunohistochemical staining was used to assess the PRTN3 levels in 47 GC tissue samples. The effects of stable lentivirus-mediated PRTN3 knockdown on GC cell proliferative, cell cycle, and apoptotic activity were evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays, nude mouse models, and flow cytometry.

Results: Elevated levels of PRTN3 messenger RNA (mRNA) and protein were noted in GC tissues, mostly in the cytosol. High PRTN3 levels were positively correlated with GC tumor N staging. in vitro knockdown of PRTN3 suppressed cell cycle progression, promoted apoptotic induction, and decreased the concentrations of cell cycle-associated proteins (cyclin D1, CDK4, and CDK6) and apoptosis-related Bcl-2 while inducing the upregulation of Bax. Downregulation of PRTN3 inhibited GC cell growth both in vitro and in mouse models.

Conclusions: Our study found that high expression of PRTN3 is associated with GC tumor N staging. And PRTN3 silencing could regulate GC progression by inhibiting the cell cycle and promoting apoptosis in GC cells, which could be a potential target for GC diagnosis and treatment.