MicroRNA-335 inhibits invasion and metastasis of prostate cancer by inhibiting glutamine metabolism pathway.

Abstract

MicroRNAs play a crucial role in regulating tumor progression and invasion. Nevertheless, the expression of miRNA-335 in prostate cancer (PCa) and its clinical significance remain unelucidated. Here, we report that miRNA-335 functions as a tumor suppressor by regulating expression of glutaminase 1 (GLS1), a key enzyme of glutamine metabolism pathway, in PCa. In this study, we show that the expression of miRNA-335 is downregulated in PCa tissues. The level of miRNA-335 is even lower in highly invasive PCa cell lines. Furthermore, enhancing the expression of miRNA-335 inhibits PCa cell migration and invasion in vitro. Additionally, we identify GLS1 as the downstream effector, governed by miRNA-335 via 3'-untranslated region, and the direct regulation is verified by dual luciferase reporter assay. MiRNA-335 interrupts glutamine catabolism by inhibiting GLS1 enzymatic activity. Overexpression of miRNA-335 markedly suppresses tumor growth of PCa in vivo. To sum up, our results indicate that miRNA-335 acts as a tumor suppressor and has an important role in restraining the metastasis of PCa cells by targeting GLS1. These discoveries indicate that miRNA-335 could serve as a new prospective therapeutic target for PCa. SIGNIFICANCE STATEMENT: miRNA-335, a metabolism-related microRNA, is a potential therapeutic target for prostate cancer by interfering with glutaminase 1 activity.