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

Zinc is a transition metal and catalytic cofactor involved in many biological processes including proliferation, development, differentiation, and metabolism. Zinc transporters (ZnTs) play a fundamental role in cellular zinc homeostasis. ZnTs are responsible of zinc efflux and are encoded by 10 genes belonging to solute carrier family 30A (SLC30A1‐10), while zinc‐regulated transporter (ZRT)/iron‐regulated transporter (IRT)‐like protein (ZIP) transporters are responsible for the influx of zinc into the cytoplasm and are encoded by 14 genes belonging to solute carrier family 39A (SLC39A1‐14). In this study, we analyzed, by transcriptome analysis, the microRNA levels of ZnT‐encoding and ZIP‐encoding genes in colorectal cancer (CRC) samples matched to normal colon tissues and in CRC cell lines. Results revealed an upregulation of specific ZnT and ZIP transcripts in CRC. Upregulation of SLC30A5, SLC30A6, SLC30A7 transcripts, encoding zinc efflux transporters ZnT5, ZnT6, ZnT7, localized on endoplasmic reticulum membranes, might be part of a coordinated transcriptional program associated to the increased activity of the early secretory pathway, while transcriptional upregulation of several specific ZIP transporters (SLC39A6, SLC39A7, SLC39A9, SLC39A10, and SLC39A11) could contribute in meeting the increased demand of zinc in cancer cells. Moreover, exon‐level analysis of SLC30A9, a nuclear receptor coactivator involved in the transcriptional regulation of Wnt‐responsive genes, revealed the differential expression of alternative transcripts in CRC and normal colonic mucosa. A strong significant increase of SLC30A5, SLC30A6, SLC30A7, and SLC30A9 transcripts (ZnT5, ZnT6, ZnT7, and ZnT9) and SLC39A6, SLC39A9, SL939A10, and SLC39A11 (ZIP6, ZIP9, ZIP10, and ZIP11) was detected in colorectal cancer (CRC). Exon‐level expression analysis of SLC30A9 revealed the differential expression of alternative transcripts in CRC and normal colonic mucosa. Upregulation of Zinc transporters is associated with high transcript level of signal transducer and activator of transcription 3, cyclins, cyclin‐dependent kinases, Wnt‐pathway, and β‐catenin responsive genes.