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

Abstract

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, NME2 (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 NME2 restored 5-FU sensitivity in 5-FU-resistant CRC cells, reduced cell survival and increased cell apoptosis; and overexpression of NME2 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 NME2 mediates chemoresistance to 5-FU in CRC and that specific NME2 inhibition could optimize 5-FU-based chemotherapy of CRC.

MiR-483-3p regulates oxaliplatin resistance by targeting FAM171B in human colorectal cancer cells

“…Total RNA from cell lines was extracted using TRIzol reagent according to a previously described method [20]. For genes detection, the samples were amplified by PCR using One…”

Identification of Potential Biomarkers and Biological Pathways for Poor Clinical Outcome in Mucinous Colorectal Adenocarcinoma

“…The increased number of ribosomal protein L30 (RPL30) may play a central role in the CRC process and in induced hepatocellular carcinoma [32,33]. The overexpression of NME2 was significantly associated with not only clinical parameters related to tumor progression, invasion, and metastasis but also resistance to 5-FU treatment [34,35]. The low expression of USP33 indicated a high recurrence risk and poor overall prognosis in advanced CRC patients [36].…”

Analysis of polymorphisms in genes associated with the FA/BRCA pathway in three patients with multiple primary malignant neoplasms

“…We compare variant genes of each patient with the genetic susceptibility of genes databases including Cancer Gene Census (CGC) database [9] and two susceptibility gene databases [10,11]. Then, to better illustrate the potential functional mechanism of the varied genes(cellular process, metabolic process, single-organism process and catalytic activity [12]), the Kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) functional enrichment analysis were carried out using the database for annotation, visualization and integrated discovery the DAVID Bioinformatics Tool [13], which consists of an integrated biological knowledge base and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. To do this, firstly, the genes involved in the functional analysis.…”