Open AccessTranscriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC 31A1 , SCO 1, and COX 11 in colorectal cancer
Author(s) -
Barresi Vincenza,
TrovatoSalinaro Angela,
Spampinato Giorgia,
Musso Nicolò,
Castorina Sergio,
Rizzarelli Enrico,
Condorelli Daniele Filippo
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12060
Subject(s) - downregulation and upregulation , biology , microarray analysis techniques , microbiology and biotechnology , transcriptome , gene , cytochrome c oxidase , gene expression , chemistry , biochemistry , mitochondrion
Copper homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones encoded by a group of genes collectively known as copper homeostasis genes ( CHG s). In this work, analysis of The Cancer Genome Atlas database for somatic point mutations in colorectal cancer revealed that inactivating mutations are absent or extremely rare in CHG s. Using oligonucleotide microarrays, we found a strong increase in mRNA levels of the membrane copper transporter 1 protein [ CTR 1; encoded by the solute carrier family 31 member 1 gene ( SLC 31A1 gene)] in our series of colorectal carcinoma samples. CTR 1 is the main copper influx transporter and changes in its expression are able to induce modifications of cellular copper accumulation. The increased SLC 31A1 mRNA level is accompanied by a parallel increase in transcript levels for copper efflux pump ATP 7A, copper metabolism Murr1 domain containing 1 ( COMMD 1), the cytochrome C oxidase assembly factors [synthesis of cytochrome c oxidase 1 ( SCO 1) and cytochrome c oxidase copper chaperone 11 ( COX 11)], the cupric reductase six transmembrane epithelial antigen of the prostate ( STEAP 3), and the metal‐regulatory transcription factors ( MTF 1, MTF 2) and specificity protein 1 ( SP 1). The significant correlation between SLC 31A1 , SCO 1 , and COX 11 mRNA levels suggests that this transcriptional upregulation might be part of a coordinated program of gene regulation. Transcript‐level upregulation of SLC 31A1 , SCO 1 , and COX 11 was also confirmed by the analysis of different colon carcinoma cell lines (Caco‐2, HT 116, HT 29) and cancer cell lines of different tissue origin ( MCF 7, PC 3). Finally, exon‐level expression analysis of SLC 31A1 reveals differential expression of alternative transcripts in colorectal cancer and normal colonic mucosa.