PRIM2 Promotes Cell Cycle and Tumor Progression in p53-Mutant Lung Cancer

Simple Summary The mutation or inactivation of tumor suppressor genes is a key driving force during tumorigenesis, among which, p53 mutation is a common feature of human cancer. Therefore, exploring the potential role of p53 mutation in the occurrence and development of tumors is a powerful support for tumor diagnosis and treatment. In this study, we found that PRIM2 expression was abnormally elevated in p53-mutated lung cancer patients, and the elevated PRIM2 promoted DNA replication, enhanced mismatch repair, activated cell cycle, and promoted lung cancer progression. Here, we first report that the expression of PRIM2 is regulated by p53, and is identified as a biomarker of lung cancer malignancy and survival prognosis. p53 is a common tumor suppressor, and its mutation drives tumorigenesis. What is more, p53 mutations have also been reported to be indicative of poor prognosis in lung cancer, but the detailed mechanism has not been elucidated. In this study, we found that DNA primase subunit 2 (PRIM2) had a high expression level and associated with poor prognosis in lung cancer. Furthermore, we found that PRIM2 expression was abnormally increased in lung cancer cells with p53 mutation or altered the p53/RB pathway based on database. We also verified that PRIM2 expression was elevated by mutation or deletion of p53 in lung cancer cell lines. Lastly, silence p53 increased the expression of RPIM2. Thus, these data suggest that PRIM2 is a cancer-promoting factor which is regulated by the p53/RB pathway. The p53 tumor-suppressor gene integrates numerous signals that control cell proliferation, cell cycle, and cell death; and the p53/RB pathway determines the cellular localization of transcription factor E2F, which regulates the expression of downstream targets. Next, we explored the role of PRIM2 in lung cancer and found that knockdown of PRIM2 induced cell cycle arrest, increased DNA damage, and increased cell senescence, leading to decreased lung cancer cell proliferation. Lastly, the positive correlation between PRIM2 and E2F/CDK also indicated that PRIM2 was involved in promoting cell cycle mediated by p53/RB pathway. These results confirmed that the expression of PRIM2 is regulated by the p53/RB pathway in lung cancer cells, promotes DNA replication and mismatch repair, and activates the cell cycle. Overall, we found that frequent p53 mutations increased PRIM2 expression, activated the cell cycle, and promoted lung cancer progression.