Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1,SCO1, and COX11 in colorectal cancer

Abstract

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.

Transcriptome analysis reveals an altered expression profile of zinc transporters in colorectal cancer

“…19 Total RNA was extracted from tissue and cell lines using RNeasy Mini Kit (cat no. 19 Total RNA was extracted from tissue and cell lines using RNeasy Mini Kit (cat no.…”

“…14 There are a growing number of studies that report the involvement of ZnTs and ZIPs in a wide variety of cancers. [16][17][18][19] At this time, no study has been undertaken to analyse the global expression of the zinc transporters in colorectal cancer (CRC) and the current study was designed to determine the expression profile of all zinc efflux and influx transporters, respectively SLC30A1 to SLC30A10 and SLC39A1 to SLC39A14 in CRC samples. 15 It is very useful to explore quantitative and qualitative differences characterizing the genetic alterations and biochemical processes in the tumor cells, the application of genome-wide technologies, microarrays, and high throughput sequencing.…”

Revealing ETC-1922159 Affected Unknown 3<em>^rd</em> order WNT10B-X-X Combinations, in Silico

“…Disruption in pathways that transport copper can cause major damages in the form of metallostasis found in tumors 45 . The pathway is regulated by copper homeostasis genes and recent transcriptome analysis of copper homeostasis genes have shown the upregulation of SLC31A1, SCO and COX11 in colorectal cancer cases 46 .…”

“…If the chain is blocked then all the intermediates on the substrate side of the block become more reduced, while all those on the oxygen side become more oxidised. 46 . It has been shown that human SCO1 and SCO2 have independent cooperative functions in copper delivery to cytochrome c oxidase (CcO) 47 , 48 & 49 .…”

Synthesis and Experimental Validation of New Designed Heterocyclic Compounds with Antiproliferative Activity versus Breast Cancer Cell Lines MCF-7 and MDA-MB-231

“…Human cancer cell line was plated in 96-well plates "Nunclon TM Microwell TM" (Nunc) and were incubated at 37 ∘ C. MTT assay was performed as reported by Barresi et al [37]. After 24 h, cells were treated with the compounds (final concentration 0.01-100 M).…”