Genome-wide transcriptional analysis of apoptosis-related genes and pathways regulated by H2AX in lung cancer A549 cells

Abstract

Histone H2AX is a novel tumor suppressor protein and plays an important role in apoptosis of cancer cells. However, the role of H2AX in lung cancer cells is unclear. The detailed mechanism and epigenetic regulation by H2AX remain elusive in cancer cells. We showed that H2AX was involved in apoptosis of lung cancer A549 cells as in other tumor cells. Knockdown of H2AX strongly suppressed apoptosis of A549 cells. We clarified the molecular mechanisms of apoptosis regulated by H2AX based on genome-wide transcriptional analysis. Microarray data analysis demonstrated that H2AX knockdown in A549 cells affected expression of 3,461 genes, including upregulation of 1,435 and downregulation of 2,026. These differentially expressed genes were subjected to bioinformatic analysis for exploring biological processes regulated by H2AX in lung cancer cells. Gene ontology analysis showed that H2AX affected expression of many genes, through which, many important functions including response to stimuli, gene expression, and apoptosis were involved in apoptotic regulation of lung cancer cells. Pathway analysis identified the mitogen-activated protein kinase signaling pathway and apoptosis as the most important pathways targeted by H2AX. Signal transduction pathway networks analysis and chromatin immunoprecipitation assay showed that two core genes, NFKB1 and JUN, were involved in apoptosis regulated by H2AX in lung cancer cells. Taken together, these data provide compelling clues for further exploration of H2AX function in cancer cells.

Resveratrol induces apoptosis of human chronic myelogenous leukemia cells in vitro through p38 and JNK-regulated H2AX phosphorylation

“…In particular, H2AX phosphorylation at Ser139 has an important role in the apoptosis of tumor cells [24,25,27] . Hence, we investigated whether resveratrol could induce H2AX phosphorylation in CML cells.…”

“…Apoptosis is almost completely blocked in H2AX -/-mouse embryo fibroblasts (MEFs). The transfection of H2AX-wt, but not H2AX-139m (Ser139 was mutated to block H2AX phosphorylation), into H2AX -/-MEFs restored the ability to Increasing evidence has also demonstrated that H2AX phosphorylation is involved in the apoptosis of tumor cells [23,25,27] . To investigate the important role of γH2AX in the resveratrol-induced apoptosis of CML cells, we assessed the effects of H2AX overexpression and knockdown on the apoptosis of CML cells.…”

Epstein-Barr Virus Essential Antigen EBNA3C Attenuates H2AX Expression

“…Moreover, H2AX was shown to induce cell cycle arrest via the p53/p21 pathway (44). In addition, knockdown of H2AX was shown to strongly suppress apoptosis in lung cancer cells (45). To elucidate the biological significance of H2AX degradation through EBNA3C in LCLs as well as to explore the underlying molecular mechanism of this DNA damage protein in EBVinduced B-cell lymphomagenesis, we used H2AX knockdown LCL1 cells compared to the control vector LCL1.…”

Genes Responsive to Elevated CO2 Concentrations in Triploid White Poplar and Integrated Gene Network Analysis

“…In the network, cycle nodes represent genes, and edges between two nodes represent interactions between genes, which are expressed by degree, where indegree represent the number of source genes of a gene and outdegree represent the number of target genes of a gene [28]. Degree measures how correlated a gene is with all other network genes.…”

“…The Signal-net analysis method was used to screen for the source gene or target gene of some gene in whole KEGG-pathway database [28]. The BC values and degrees of genes are the key attributes of a network; they show the tendency of genes to interconnect with others and were used to seek out major target genes.…”