Expression Of RBBP4in Colon Carcinoma And Its Underlying Mechanisms

Backgroud/aims:Retinoblastoma binding protein4(RBBP4) is a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. RBBP4is reported to present in many protein complexes involved in histone acetylation and chromatin assembly. Moreover, expression of RBBP4was found alterative in thyroid cancer, primary hepatocellular carcinoma, lung cancer, acute myelogenous leukemia and breast cancer. RBBP4is closely related with tumorigenesis, and affected the curative effect of radiotherapy and chemotherapy on tumor. However, there is little knowledge about the expression and roles of RBBP4in colon cancer. In the present study, we aimed to investigate the expression of RBBP4in colon cancer, and explore its potential roles and mechanisms.Methods:The expression of RBBP4was examined in52paired colon tissues by immunohistochemistry (IHC). RBBP4overexpression was constructed and knockdown stably transfected SW620cell lines by leti-virus vectors. Then the effect of RBBP4on cell proliferation, invasion, migration and apoptosis were tested by CCK-8method, transwell invasion and migration assay, and flow cytometry, respectively. The nude mouse tumorigenicity assay was used to investigate the effect of RBBP4on colon cancer cell proliferation in vivo. Finally, the potential mechanism of RBBP4on colon cancer progression was explored.Results:The expression of RBBP4in colon cancer tissues was significantly up-regulated compared with para-cancer issues, and over-expression of RBBP4was correlated with tumor TNM stage (P=0.002), lymphatic metastasis (P=0.000), invasive depth (P=0.001). Knockdown of RBBP4significantly inhibited cell proliferation, invasion, migration, but promoted colon cancer cell apoptosis. In contrast, over-expression of RBBP4significantly promoted cell proliferation, invasion, migration, but suppressed colon cancer cell apoptosis. Nude mouse tumorigenicity assay showed that over-expression of RBBP4could obviously facilitate tumorigenesis and progression. Compared with knockdown of RBBP4, the tumor size was significantly bigger and weight was significantly heavier in over-expression of RBBP4. Over-expression of RBBP4inhibited colon cancer cell apoptosis mainly via Bcl-2apoptosis pathway to damage mitochondria apoptosis.Conclusions:Our study reveals that RBBP4might play an important role on colon cancer cell proliferation, invasion, migration, and cell apoptosis. RBBP4could promote colon cancer progression by inhibiting cell apoptosis via Bcl-2signal pathway. However, RBBP4-based colon cancer therapy needs further investigation.