H2A/K pseudogene mutation may promote cell proliferation

Publication date: Available online 2 March 2016 Source:Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Author(s): Jisheng Guo, Ruirui Jing, Xin Lv, Xiaoyue Wang, Junqiang Li, Lin Li, Cuiling Li, Daoguang Wang, Baibing Bi, Xinjun Chen, Jinghua Yang 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 lncRNAs affected cell proliferation. Quantitative proteomic analysis indicated that the expression of mutant H2A/K lncRNAs 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 lncRNAs. Western blotting confirmed the critical upregulation of PCNA by mutant H2A/K lncRNA expression. Finally, the promotion of cell proliferation by mutant H2A/K lncRNAs (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 lncRNAs, we confirmed that the mutant H2A/K lncRNAs promoted cell prolifer...

Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - March 2, 2016 Category: Cytology Source Type: research