The role of c-Myc-RBM38 loop in the growth suppression in breast cancer

Background: rna-binding protein 38 (rbm38) is a member of the rna recognition motif (rrm) family of rna-binding proteins (rbps). rbm38 often exerts its function by forming regulatory loops with relevant genes. c-myc is an oncogenic transcription factor that is upregulated in one-third of breast cancers and involved in many cellular processes in this malignancy. in our previous study,rbm38 was identified as a tumor suppressor in breast cancer. in the present study,we investigated the mechanisms underlying the regulation of this tumor suppressor. methods: lentivirus transfections,western blotting analysis,qrt-pcr and immunohistochemistry were employed to study the expression of c-myc and rbm38. chromatin immunoprecipitation and dual-luciferase reporter assays were performed to investigate the direct relationship between c-myc protein and the rbm38 gene. rna immunoprecipitation combined with dual-luciferase reporter assays was conducted to confirm the direct relationship between the rbm38 protein and the c-myc transcript. results: knockdown of c-myc increased rbm38 expression by binding directly to specific dna sequences (5'-cacgtg-3'),known as the e-box motif,in the promoter region of rbm38 gene. additionally,rbm38 destabilized the c-myc transcript by directly targeting au-rich elements (ares) in the 3'-untranslated region (3'-utr) of c-myc mrna to suppress c-myc expression. moreover,specific inhibitors of c-myc transcriptional activity inhibited rbm38-induced suppression of growth,implying that rbm38 acts as a tumor suppressor via a mechanism that depends,at least partially,on the reduction of c-myc expression in breast cancer. conclusions: rbm38 and c-myc form a unique mutually antagonistic rbm38-c-myc loop in breast cancer. © 2017 the author(s).