Regulate the effects of CST1 on cell proliferation,migration,invasion and cell cycle of breast cancer

WANG Jian; Lyu Xu; SHAO Rongjin; SHI Meijie; TAO Shuang

doi:10.3969/j.issn.1674-4136.2025.04.010

Abstract：Objective To investigate the regulatory effect of cysteine protease inhibitor(CST1)on proliferation,migration,invasion and cycle of breast cancer cells and its potential mechanism.Methods The UALCAN and GEPIA databases were used to analyze the expression levels of CST1 in different cancer tissues in the Cancer Gene Atlas(TCGA)database.The expression level of CST1 in breast cancer and its relationship with clinical features and survival prognosis were further analyzed.Signaling pathway enrichment analysis of CST1 was performed by CANCERTOOL and GeneCards databases.The correlation between CST1 and cell cycle-related proteins(P21,P27,CyclinD1 and CDK1)was analyzed based on Metabric database.MDA-MB-231 cells were divided into four groups:OE-NC group(high expression control group),OE-CST1 group(high expression group),sh-NC group(low expression control group),and sh-CST1 group(low expression group).CCK-8,scratch assay and Transwell assay were used to detect the effects of CST1 on cell proliferation,migration and invasion.Western blot was used to detect the expression levels of CST1 and its downstream proteins(P21,P27,CyclinD1,CDK1).Results The analysis results of public databases indicated that CST1 was abnormally expressed in various tumor tissues,and the expression of CST1 in breast cancer was higher than that in nomal tissues(P<0.05),and was positively correlated with age,lymph node metastasis and clinical stage(P<0.05),and the overall survival of patients with high expression of CST1 was worse(P<0.05).Pathway enrichment analysis showed that the cell cycle signaling pathway was at the forefront,and was correlated with P21,P27,CyclinD1,and CDK1(P<0.05).The results showed that high expression of CST1 promoted the proliferation,migration and invasion of breast cancer cells,(P<0.05),However,low expression of CST1 inhibited the above phenotype(P<0.05).The result of western blot assay showed that the protein level of CST1 in breast cancer cells in the low expression group was significantly lower than that in the high expression group(P<0.05).In addition,the protein levels of P21 and P27 significantly decreased in the CST1 high expression group,and the protein levels of CyclinD1 and CDK1 increased significantly(P<0.05).However,the low expression group of CST1 showed the opposite trend.Conclusions The expression of CST1 can regulate the proliferation,migration,invasion ability of breast cancer cells,and can also target regulate the expression of P21,P27,CyclinD1and CDK1,thereby affecting the breast cancer cell cycle.