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SLC30A and SLC39A Family Members are targeted by MicroRNAs that also target genes within the Transforming Growth Factor‐β Signaling Pathway
Author(s) -
Grider Arthur
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.967.16
Subject(s) - kegg , biology , gene , microrna , genetics , transforming growth factor , gene expression , microbiology and biotechnology , transcriptome
Zinc is essential for normal growth and development in humans; and deficiency causes impaired growth. The SLC30A (cation diffusion; ZNT) and SLC39A (zrt/irt‐like proteins; ZIP) gene families encode zinc transporters necessary for maintaining cellular zinc homeostasis. ZNT gene products transport zinc out of the cytosol while the ZIP gene products transport zinc into the cytosol. Hence, they are responsible for cellular zinc uptake or secretion, and intracellular compartmentalization. The Transforming Growth Factor‐β (TGF‐β) signaling pathway is involved in numerous cellular processes, including bone development and osteoblast differentiation. The purpose of this study was to determine whether microRNAs (miRNA) that are predicted to target the zinc transporter genes (SLC30A contains 10 members; SLC39A contains 14 members) also target genes within the TGF‐β signaling pathway. Each zinc transporter gene member was used to query the miRDB.org database to identify miRNAs predicted to target them. Those miRNAs which exhibited target prediction scores ≥81 were then used to query the DIANA TOOLS mirPath v.3 database to identify the genes that they are predicted to target within the Kyoto Encyclopedia of Genes and Genomes (KEGG) hsa04350 TGF‐β signaling pathway. At total of 366 miRNAs are predicted to target 23 of the 24 Zn transporter mRNAs (there are six miRNAs that are predicted to target SLC39A4 (ZIP4) mRNA, however the target prediction scores range from 76 to 52; SLC39A4 was excluded from further analyses). There were 7 zinc transporter genes that were predicted to be targets for 20 or more miRNAs (SLC30A: ZNT4, ZNT5, ZNT7; SLC39A: ZIP8, ZIP9, ZIP10, ZIP14). ZNT5 and ZIP9 were predicted to be targeted by 55 and 52 miRNAs, respectively. A total of 2048 mRNA targets are contained within 76 TGF‐β signaling pathway genes. 37 genes are targeted by 20 or more miRNAs; 25 genes are targeted by 30 or more miRNAs; 18 genes are targeted by 30 or more miRNAs. There were two genes within the TGF‐β signaling pathway that were predicted to be targets for more than 100 miRNAs, activin receptor type 2B and bone morphogenetic protein receptor type II. The results indicate that there is significant overlap between the miRNAs that target the members of the zinc transporter gene families and those that target genes within the TGF‐β signaling pathway. Support or Funding Information USDA NIFA Hatch GEO00794