LAUSR

Dear Editor, Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death for men in the United States [1]. PCa with similar Gleason score has been reported to show substantial interpatient heterogeneity and differential prostate cancer-specific mortality rate [2]. Such heterogeneity in PCa often results in different therapeutic responses among patients, including therapy resistance, therapeutic failure, relapse, and metastasis [3]. Numerous oncogenes, such as eukaryotic translation initiation factor 4E (eIF4E), have been reported to be involved in epithelial-mesenchymal transition (EMT) and/or drug resistance in PCa [4]. We previously demonstrated that eIF4E overexpression was involved in chemoresistance of triple-negative breast cancer and silencing eIF4E significantly inhibited cancer cell proliferation and sensitized cancer cells to chemotherapy in a patient-derived xenograft mouse model [5]. In addition, eIF4E phosphorylation is known to stimulate the translation of matrix metalloproteinase 3 (MMP3) and Snail mRNAs to promote EMT in PCa [6]. Furthermore, the complexity and dynamic nature of EMT contributes to the heterogeneity of aggressive cancer cells [7]. The precise role of eIF4E in EMT, invasion, and chemoresistance in PCa is still to be established with consideration of different subpopulations in order to develop precision medicine for PCa. In this work, we aimed to explore the role of eIF4E in EMT, invasion, and chemoresistance in PCa for establishing a promising new therapeutic strategy by regulating eIF4E expression using (1-aminoethyl)iminobis[Noleicylcysteinyl-1-aminoethyl) propionamide] (ECO)/small interfering RNA (siRNA) nanoparticles previously developed in our lab [8-10] for PCa therapy in the context of tumor heterogeneity. Two PCa cell lines (PC3 and DU145) and their corresponding paclitaxel (PTX)-resistant cell lines (PC3-DR and DU145-DR) were investigated to assess the role of eIF4E