GO classification.

<p>Annotation statistics of differentially expressed genes in the secondary node of GO. The horizontal axis shows the secondary nodes of three categories in GO. The vertical axis displays the percentage of annotated genes versus the total gene number. The red columns display annotation information of the total genes and the blue columns represent annotation information of the differentially expressed genes only.</p

Cell morphology differences between A549 and A549/DDP cells.

<p>Micrographs showing A549 and A549/DDP cells cultured for 3 days in the absence or presence of cisplatin (10μg/mL).</p

The inhibitory effects of different concentrations of cisplatin (DDP) on A549 and A549/DDP cells.

<p>Cell viability, as assessed by the CCK-8 assay, was determined 24 h after exposure of A549 or A549/DDP cells to increasing amounts of cisplatin. Results represent the average of triplicate wells and are representative of three independent experiments. Black bars and symbols, A549/DDP; red bars and symbols, A549.</p

Statistical summary of transcriptome sequencing.

<p>Statistical summary of transcriptome sequencing.</p

Significant deregulated key signaling nodes of most DEGs enriched pathways.

<p>Significant deregulated key signaling nodes of PI3K/AKT, MAPK, Focal Adhesion and Actin Cytoskeleton pathway.</p

COG function classification of the consensus sequences.

<p>The COG categories are shown on the horizontal axis and gene numbers and proportions are plotted on the vertical axis.</p

KEGG categories of HepG2/DDP cells DEGs.

<p>The vertical axis lists the names of the metabolic pathways in the KEGG database, and the horizontal axis shows the proportion of annotated genes in each pathway versus the total number of annotated genes.</p

Distribution of the differentially expressed genes shown as a volcano plot.

<p>Each point represents a gene. The green dots represent the down-regulated differentially expressed genes, red dots represent the up-regulated differentially expressed genes, and black dots represent non-differentially expressed genes.</p

Nucleoside diphosphate kinase 2 confers acquired 5-fluorouracil resistance in colorectal cancer cells

<p>Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. 5-fluorouracil (5-FU)-based chemotherapeutic regimens are routinely used for the treatment of patients with CRC. However, recurrence and chemotherapeutic drug resistance limit the survival rates of patients with CRC. DNA methylation participates in diverse cellular processes by regulating the transcription of a large number of genes expression, cell division, apoptosis, cell adhesion and differentiation, and metabolism, thus it might mediate chemoresistance. Using an Illumina Infinium HD Assay, DNA methylation levels in a human 5-FU-resistant HCT-8 CRC cell line (HCT-8/FU) and its progenitor cell line HCT-8 were analysed. A total of 16,580 differentially methylated genes were identified, of which 8885 were hypermethylated and 7695 were hypomethylated in resistant cells. Among these genes, <i>NME2</i> (nucleoside diphosphate kinase 2) exhibited a significant difference in methylation between cell lines and has known roles in gastric cancer and breast cancer; accordingly, we hypothesized that it plays a role in acquired resistance in CRC. Knockdown of <i>NME2</i> restored 5-FU sensitivity in 5-FU-resistant CRC cells, reduced cell survival and increased cell apoptosis; and overexpression of <i>NME2</i> in HCT-8 cells results in the acquisition of resistance to 5-FU, this alteration enhanced HCT-8 cells growth abilities and reduced apoptosis. These findings suggest that <i>NME2</i> mediates chemoresistance to 5-FU in CRC and that specific <i>NME2</i> inhibition could optimize 5-FU-based chemotherapy of CRC.</p