title: H2A/K pseudogene mutation may promote cell proliferation.
abstract: 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 proliferation by upregulating PCNA and other oncogenes. The hypothesis that cell proliferation is promoted by the mutant H2A/K lncRNAs was supported by the protein expression and cell proliferation assay results. Therefore, mutant H2A/K lncRNAs may be a new factor in renal carcinogenesis.
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Jisheng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Jing
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lv
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Junqiang
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Li
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Daoguang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Baibing
authors.initials: B
authors.lastname: Bi
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xinjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan 250012, China; Department of Surgery, VA Boston Healthcare System, Boston University School of Medicine, Boston 510660, MA, USA. Electronic address: sdu_crc_group1@126.com.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D015870:Gene Expression; D063990:Gene Ontology; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D017354:Point Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D060066:Protein Interaction Maps; D011544:Pseudogenes; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D062085:RNA, Long Noncoding
keywords: Cell proliferation; H2A/K; LncRNA; Quantitative proteomics