H2A/K pseudogene mutation may promote cell proliferation

Little attention has been paid to the histone H2A/K pseudogene. Results from our laboratory showed that 7 of 10 kidney cancer patients carried a mutant H2A/K pseudogene; therefore, we were interested in determining the relationship between mutant H2A/K and cell proliferation. We used shotgun and label-free proteomics methods to study whether mutant H2A/K IncRNAs affected cell proliferation. Quantitative proteomic analysis indicated that the expression of mutant H2A/K IncRNAs resulted in the upregulation of many oncogenes, which promoted cell proliferation. Further interaction analyses revealed that a proliferating cell nuclear antigen (PCNA)-protein interaction network, with PCNA in the center, contributes to cell proliferation in cells expressing the mutant H2A/K IncRNAs. Western blotting confirmed the critical upregulation of PCNA by mutant H2A/K IncRNA expression. Finally, the promotion of cell proliferation by mutant H2A/K IncRNAs (C290T, C228A and A45G) was confirmed using cell proliferation assays. Although we did not determine the exact mechanism by which the oncogenes were upregulated by the mutant H2A/K IncRNAs, we confirmed that the mutant H2A/K IncRNAs promoted cell proliferation by upregulating PCNA and other oncogenes. The hypothesis that cell proliferation is promoted by the mutant H2A/K IncRNAs was supported by the protein expression and cell proliferation assay results. Therefore, mutant H2A/K IncRNAs may be a new factor in renal carcinogenesis. (C) 2016 Elsevier B.V. All rights reserved.