Background: Lung cancer is the second most prevalent type of cancer worldwide; however, its death is the highest among all cancers. Previous studies have shown that MEX3A is associated with Argonaute (Ago) and CDX2 proteins, which are important in tumor progression. High expression of MEX3A is also known to negatively affect the therapeutic impact of radiotherapy and chemotherapy. Therefore, we investigated the role of MEX3A in non-small cell lung cancer (NSCLC).
Methods: Tumor specimens were collected from 87 NSCLC patients who underwent surgical resection between 2014 and 2019 at the Pathology Archive of the First Affiliated Hospital of China Medical University, and were subsequently used for immunohistochemistry. NSCLC cell lines and normal bronchial epithelial HBE cell line were used to study the effects of MEX3A by utilizing MEX3A-siRNA, MEX3A-plasmids, and the ERK pathway inhibitor U0126. Western blotting, colony formation assays, MTT assays, and Transwell assays with or without Matrigel were performed to explore the impact of MEX3A on NSCLC.
Results: MEX3A protein expression was associated with tumor differentiation (P=0.044), size (P=0.020), lympth node status (P=0.001), and p-TNM stage (P=0.009) and was preferentially expressed in tumor tissues. MEX3A was found to be localized to the nucleus. The expression level in cancer tissue was significantly higher than that in normal tissue. According to our study, MEX3A was shown to promote the proliferation, migration, and invasion of NSCLC. In addition, MEX3A regulated the expression of P-MEK, P-ERK, CyclinA2, CDK4, CDK6, RhoA and MMP2. The MEK inhibitor U0126 reduced the biological effects of MEX3A , suggesting that MEX3A increases the carcinogenic activity of NSCLC cells through activation of the MEK/ERK signaling pathway.
Conclusion: These results suggest an association between MEX3A expression and the unfavorable clinicopathological characteristics of NSCLC patients. And MEX3A promote NSCLC progression by increasing the proliferative and metastatic potential of cancer cells through upregulation of the MEK/ERK pathway. We propose that MEX3A is a candidate prognostic biomarker and potential therapeutic target in NSCLC.