RESUMEN
Colon cancer is associated with high death rates worldwide and poses a serious threat to public health. GINS complex subunit 2 (GINS2) serves a carcinogenic role in many cancers, including gastric adenocarcinoma, ovarian cancer and pancreatic cancer. However, the specific function of GINS2 in the development of colon cancer has not been described in detail. The present study aimed to clarify the role of GINS2 in colon cancer. A Cell Counting Kit8 assay, EdU staining, TUNEL and flow cytometry analyses were performed to determine the levels of cell viability, proliferation and apoptosis and to evaluate the cell cycle. Through the analysis of BioGrid, a ProteinProtein Interaction database, it was hypothesized that protein tyrosine phosphatase 4A1 (PTP4A1) is a protein that might interact with GINS2, which was then validated using a coimmunoprecipitation assay. mRNA and protein levels were measured using reverse transcriptionquantitative PCR and western blotting, respectively. The results of the present study demonstrated that GINS2 expression levels were increased in colon cancer cells. Furthermore, GINS2 knockdown inhibited the proliferation of colon cancer cells, while the levels of cell cycle arrest and apoptosis were increased. By interacting with PTP4A1, GINS2 promoted the expression of PTP4A1, a novel p53 target. GINS2 knockdown was increased, while PTP4A1 overexpression decreased the protein level of p53. Notably, PTP4A1 overexpression partly reversed the effects of GINS2 downregulation on colon cancer cells. Therefore, the present study demonstrated that GINS2 regulated the proliferation and apoptosis of colon cancer cells through PTP4A1/p53 pathway, highlighting that GINS2 may serve as a novel molecular marker for colon cancer prevention and therapy.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Neoplasias del Colon/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Línea Celular , Proliferación Celular/genética , Proteínas Cromosómicas no Histona/genética , Neoplasias del Colon/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , Proteínas Tirosina Fosfatasas/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Globally, thyroid cancer (TC) is considered to be the commonest endocrine malignancy. GINS complex subunit 2 (GINS2) belongs to the GINS complex family and is associated with cellular migration, invasion and growth. The present study aimed to investigate the underlying mechanisms of GINS2 on cell viability, migration and invasion in TC cells. By using MTT, wound healing and Transwell assays, the cell viability, migration and invasion were determined. Apoptosis was examined by immunofluorescence. Western blotting was used to detect protein expression levels. In the present study, biological function analysis demonstrated that GINS2 interference attenuated cell viability, migration and invasion in TC cell lines (K1 and SW579). It was discovered that, compared with the control group, GINS2 silencing induced apoptosis in TC cells. Additionally, GINS2 interference inhibited key proteins in the MAPK signaling pathway, including JNK, ERK and p38. According to these comparative experiments, GINS2 was considered to act a pivotal part in cell viability, migration and invasion of TC by regulating the MAPK signaling pathway and might be a potential therapeutic target for treating TC.