Receptor-interacting protein kinase 3 is a predictor of survival and plays a tumor suppressive role in colorectal cancer

Xiaodong Feng, Qi Song, Ailian Yu, Huamei Tang, Zhihai Peng,  Xuechun Wang

Abstract:

Background Receptor-interacting protein kinase 3 (RIP3) is a member of the RIP Ser/Thr kinase family which as a key signaling molecular to play an important role in regulate the pathway of cell survival, cell apoptosis and cell necrosis. However, the role of RIP3 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods We used quantitative PCR and Western blot analysis to examine RIP3 level of mRNA and protein in primary colorectal cancer and paired normal colonic mucosa respectively. RIP3 clinicopathological significance was assessed by immunohistochemical staining in which 112 cases of primary colorectal cancer paired with noncancerous tissues. The biological function of RIP3 overexpression was measured by CCK8 assay, plate colony formation assay. Dual staining with fluorescent Annexin V and propidium iodide (PI) have been used to discriminate apoptotic or necrotic cell death. Results RIP3 expression is significantly lower in colorectal cancer and associated with T stage, M stage and AJCC stage. Cox proportional hazard models showed that RIP3 expression was an independent prognostic factor for overall survival and disease-free survival in patients with colon cancer. Overexpression of RIP3 significantly suppressed the proliferation of colon cancer cells in vitro by its ability to induce apoptosis. Conclusions Our clinical and experimental data suggest that RIP3 may play a suppressive role in the colorectal carcinogenesis. And our study may provide a new therapeutic target for colorectal cancer treatment.