RBMS2 Inhibits The Proliferation By Stabilizing P21 MRNA In Breast Cancer

Background:RNA binding proteins(RBPs)play an important role in regulating the metabolism of target RNA.Aberrant expression of RBPs plays a vital role in the initiation and development of cancer.The RBMS family,which has the conserved RNA binding motif RNP1 and RNP2,shares the similar function in RNA processing and RBMS2 is a member of them.P21,also named CDKN1A,promotes cell cycle arrest and plays an important role in halting cell proliferation.In our study,we proved RBMS2 as a tumor suppressor in breast cancer and it inhibited the proliferation of breast cancer by positively regulated the stability of P21 mRNA in a posttranscriptional way.Methods:TCGA was used to identify differentially expressed RBPs in breast cancer.The effects of RBMS2 depletion or ectopic expression on breast cancer proliferation were evaluated in vitro using CCK-8 assays,colony formation assays and cell-cycle assays and the in vivo effects were investigated using a mouse tumorigenicity model.The main pathway and genes regulated by RBMS2 was detected by RNA sequence.The RNA immunoprecipitation combined with dual-luciferase reporter assay were conducted to testify direct relationship between RBMS2 and P21.Results:The expression of RBMS2 was lower in breast cancer compared with normal tissues and was a favorable biomarker in breast cancer.RBMS2 inhibited the proliferation of breast cancer and P21 was the main target of RBMS2.RBMS2 stabilized the mRNA of P21 by directly binding to the 3'UTR region.Anti-proliferation activity induced by overexpression of RBMS2 was rescued by interfering with the expression of P21Conclusion:In conclusion,RBMS2 acts as a tumor suppressor in breast cancer and positively regulated the expression of P21 by stabilizing the mRNA.