Abstract

Lung cancer, with high death rate and incidence rate, is one of the top three lethal cancers worldwide. Present therapies can bring little benefit for patients with recurrence and metastasis, which is due to the heterogeneity and complicated mechanism underlying lung cancer. PDIA2 is reported to promote cancer progression. However, its role in lung cancer is not clear. According to the TCGA, PDIA2 was expressed much higher in lung cancer tissues (n = 515) than that in normal tissues (n = 59). And the survival probability of patients with high PDIA2 expression was much worse than that with low PDIA2 expression (p = 0.022). The median survival time of patients with high PDIA2 expression was 65.1 months but it was 75.43 months in patients with low PDIA2 expression. In lung cancer cells, PDIA2 also demonstrated higher expression than that in BEAS-2B cells. When PDIA2 was decreased in lung cancer cells, the ability of cell proliferation and migration was inhibited. In contrast, cell apoptotic rate was increased. However, overexpression of PDIA2 promoted cell proliferation and migration. In addition, the level of the MT membrane potential was decreased significantly while the ROS level was increased. Moreover, PDIA2 knockdown caused significant decrease of critical members in JNK signaling pathway such as JNK, c-Jun, and smad4 while PDIA2 overexpression exhibited reversed effects. And the expression levels of cleaved caspase-3, bax, and bcl-2 were affected by PDIA2. These data suggest that PDIA2 regulated both the JNK signaling and caspase-3 cascade response in lung cancer. In addition, the IC50 of Carboplatin in lung cancer cells was declined when PDIA2 was knocked down, which suggests the increased efficacy of Carboplatin. In summary, PDIA2 contributes to the progression of lung cancer and JNK and caspase-3 signaling pathway play important roles, which proposes PDIA2 as a potential target for therapy of lung cancer.