Long Non-Coding RNA FAM66C Promotes Prostate Cancer Metastasis via JNK-Mediated Proteasome and Lysosomal Pathway

Abstract

Purpose To identify the role of long non-coding RNA FAM66C in the metastatic progression of prostate cancer cells and its underlying mechanisms. Methods The Cancer Genome Atlas (TCGA) data was utilized to determine the relative expression of lncRNA FAM66C in prostate cancer patients with lymph node metastasis. Knockdown FAM66C by siRNA was performed to investigate the effects of FAM66C in cell migration and epithelial-mesenchymal transition (EMT) by wound healing assay and Western blotting. The proteasome inhibitor MG132 and lysosomal inhibitor chloroquine (CQ) were used to determine the effect of these pathways in FAM66C-regulated cell migration. The c-jun-N-Terminal Kinase (JNK) inhibitor SP600125 was used to identify the role of JNK signaling in FAM66C-regulated cell migration and the proteasome and lysosome pathways. Results A lower expression of lncRNA FAM66C was noted in the most prostate cancer patients. Knockdown of FAM66C in human prostate cancer DU145 and PC-3 cells promoted EMT and cell migration, which was suppressed by proteasomal inhibitor MG132 and lysosomal inhibitor CQ. Knockdown of FAM66C induced JNK signaling, cell migration and invasion, and activation of proteasome and lysosome pathways were suppressed by JNK inhibitor SP600125. Conclusion This study provided new evidence of the role of lncRNA FAM66C in the regulation of JNK signaling mediated proteasome and lysosome pathways affecting migration ability of prostate cancer cells.