The RNA Binding ProteinRBMS3 Suppresses Metastasis Of Breast Cancer By Regulating Twist1 Expression

Backgrounds: Breast cancer metastasis is responsible for the low overall survival rate of patients and remains the biggest obstacle for breast cancer treatment.Therefore,identification of specific biomarker of metastasis is very necessary.The RNA binding motif single stranded interacting protein 3(RBMS3)acts as a tumor suppressor in various cancers,Whereas its role and underlying molecular mechanism in breast cancer remains fragmentary.Methods:SUM-1315 and MDA-MB-231 breast cancer cells were transfected with lentivirus to knockdown or overexpress RBMS3 expression.Quantitative real-time PCR(qRT-PCR)and western blots were performed to testify the transfection efficiency in protein and mRNA level.Western blot and qRT-PCR were carried out to determine expression of RBMS3 in breast cancer cells and tissues.Transwell and experimental metastasis assay were conducted to investigate the effects of RBMS3 on migration and metastasis.Transcriptome sequencing was applied to identify the differential genes expression in RBMS3.RNA immunoprecipitation assay combined with luciferase reporter assay were performed to explore the direct correlation between RBMS3 and Twist1.cells that overexpress RBMS3 and the control were transfected with Twist1-overexpressing lentivirus to examine the effects on cell migration and lung metastasis.Results: RBMS3 was downregulated in the primary breast cancer cells and tissue.Ectopic expression of RBMS3 contributed to inhibition of cell migration in vitro and lung metastasis in vivo.Furthermore,RBMS3 could negatively regulate Twist1 expression via directly binding to 3'-UTR of Twist1 mRNA,and thereby decrease Twist1-induced expression of matrix metalloproteinase 2(MMP2).Additionally,Twist1-induced cell migration and lung metastasis could be reversed by the overexpression of RBMS3 in vitro and in vivo Conclusions: In summary,our study revealed a novel mechanism of the RBMS3/Twist1/MMP2 axis in the regulation of invasion and metastasis,which may become a potential molecular marker for breast cancer prevention and treatment.