Cyclophilin J inhibited oxidative stress and apoptosis in triple-negative breast cancer cell through activating the PI3K/Akt signaling pathway

Abstract

Triple-negative breast cancer (TNBC) was a highly aggressive and metastatic subtype of breast cancer characterized by a poor prognosis and limited treatment options. Clarifying the underlying molecular mechanisms was of significant clinical importance. In this study, we plotted Kaplan-Meier survival curves based on data from the Human Cancer Database and found that elevated CYPJ expression increased patient mortality risk and decreased survival rates. CYPJ was expressed at low levels in normal breast epithelial cells but was highly expressed in various TNBC, particularly in MDA-MB-231 and BT-549 cell lines. Subsequently, we employed lentiviral transfection technology to induce overexpression or knockdown of CYPJ in these two cell lines and validated the transfection efficiency using RT-qPCR and Western blot. The results showed that CYPJ overexpression promoted TNBC cell proliferation, facilitated the transition of the cell cycle from the G0/G1 phase to the S phase, and increased the activity of superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPX). Additionally, it inhibited apoptosis and reduced the production of reactive oxygen species (ROS) and malondialdehyde (MDA). To further investigate the mechanism of action, a BT-549 tumor-bearing mouse model was established, and the pathway inhibitor MK2206 was administered. The results showed that MK2206 could reverse the pro-proliferative and anti-apoptotic effects of CYPJ overexpression, while also diminishing its protective effect against oxidative stress-induced damage. In summary, this study concluded that CYPJ functioned as an oncogene in TNBC. CYPJ overexpression promoted TNBC progression by activating the PI3K/Akt signaling pathway, inhibiting cellular oxidative stress responses, and suppressing apoptosis.