PTEN Expression Is Up-regulated By RBM38 Via Enhancing Its MRNA Stability In Breast Cancer

Objective:To explore the mechanism of PTEN regulated by the RNA binding protein RBM38 in breast cancer and the role of PTEN in RBM38-mediated growth suppression.Materials and methods:RIP-seq(RNA Immunoprecipitation and sequencing)was used to identify RBM3 8-bound genes.Immunohistochemistry,lentivirus transfections,Western blotting analysis,qRT-PCR and ELISA were used to conduct the relation between RBM38 and PTEN.RNA immunoprecipitation,RNA electrophoretic mobility shift and dual-luciferase reporter assays were employed to identify the direct binding sites of RBM38 with PTEN transcript.Colony formation assay was conducted to confirm the function of PTEN in RBM38-induced growth suppression.Results:The results of RIP-seq shown that PTEN might bind directly to RBM38.PTEN expression was positively associated with the expression of RBM38 in breast cancer tissues and breast cancer cells.Moreover,RBM38 stabilized PTEN transcript to enhance PTEN expression via binding to multiple AU/U-rich elements(AREs)in 3'-untranslated region(3'-UTR)of PTEN transcript.Additionally,specific inhibitors of PTEN activity and small interfering(siRNA)of PTEN expression inhibited RBM38-mediated suppression of proliferation,which implied that RBM3 8 acted as a tumor suppressor partly by enhancing PTEN expression.Conclusions:RBM38 expression was significantly correlated with PTEN in breast cancer.PTEN expression and activity was increased by ectopic overexpression of RBM38,while RBM38 down-regulation decreased PTEN expression and activity.RBM38 could increase the expression of PTEN by binding the AU/U-rich regions of 3'-UTR of PTEN mRNA directly.RBM38 could regulate the PTEN mRNA stability.RBM3 8 was a positive post-transcriptional regulator of PTEN expression and the proliferation meditated by RBM38 was partialy effected by the expression of PTEN.