Ring Finger Protein 43 Research Articles

Ring Finger Protein 43 as a New Target for Cancer Immunotherapy

We have performed genome-wide exploration by using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes (CTLs) specific to tumor cells. In our preceding study, we identified multiple new genes by using gene expression profiling with a genome-wide cDNA microarray containing 23,040 genes. Among them, we selected RNF43 (ring finger protein 43) as a promising candidate for a TAA expressed by colon cancer cells. In this study, we examined whether the RNF43 protein contains antigenic epitope peptides restricted to HLA-A*0201 or HLA-A*2402. The CTL clones were successfully induced with stimulation by using the peptides binding to HLA-A*0201 (ALWPWLLMA and ALWPWLLMAT) and HLA-A*2402 (NSQPVWLCL), and these CTL clones showed the cytotoxic activity specific to not only the peptide-pulsed targets but also the tumor cells expressing RNF43 and respective HLAs. Lytic activities mediated by two HLA-A2-restricted epitopes were marginal, whereas tumor lysis mediated by the HLA-A24 epitope was clearly better. These findings might be caused by the poor natural presentation of RNF43-11(IX) and RNF43-11(X) by tumors or poor T-cell receptor avidity for these specific epitopes. These results strongly suggest that RNF43 is a new TAA of colon cancer. Furthermore, these results also suggest that our strategy might be a promising one to efficiently discover clinically useful TAAs.

A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer

We previously analyzed expression profiles of 20 colorectal tumors by means of genome-wide cDNA microarray. Among the genes that were commonly up-regulated in the CRCs, we further characterized biological importance of a novel human gene termed RNF43 (RING finger protein 43) in colorectal carcinogenesis. Multiple-tissue northern blot analysis revealed undetectable expression of RNF43 in normal adult tissues examined and low levels of expression in fetal kidney and lung. Its exogenous expression conferred a growth-promoting effect in COS7 and NIH3T3 cells, and suppression of its expression by specific short interfering RNAs retarded the growth of colon cancer cells. Interestingly, RNF43 protein was shown to be a secreted protein, and addition of the conditioned media of the RNF43-transfected cells into culture media of NIH3T3 cells revealed a significant enhancement of cell growth. These data suggest that RNF43 may exert its growth promoting effect in an antocrine manner, and that it may be a novel diagnostic marker for colorectal cancer.