A miR-511-binding site SNP in the 3'UTR of IGF-1 gene is associated with proliferation and apoptosis of PK-15 cells

In Vitro Cell Dev Biol Anim. 2019 May;55(5):323-330. doi: 10.1007/s11626-019-00329-4. Epub 2019 Apr 3.

Abstract

Insulin-like growth factor-1 (IGF-1) is a functional candidate gene for pig growth and development due to its crucial role in the growth axis of growth hormone-IGF-1. Considering that the 3' untranslated region (3'UTR) of gene may affect its expression, we analyzed the effect of a single-nucleotide polymorphism (SNP) (rs34142920, c.674C > T) on gene expression, cell proliferation, and apoptosis and the possible related molecular mechanisms in PK-15 cells. The SNP was found in the 3'UTR of IGF-1 in Bama Xiang pig in previous investigations. Results showed that the SNP was located at the target site binding to microRNA (miR-511). The 3'UTR of IGF-1 gene with C allele significantly downregulated the expression of IGF-1 gene compared with that of the gene with T allele by luciferase assay. miR-511 was transfected into porcine kidney cell line (PK-15 cells) to reveal its effects on cells and whether or not it targets IGF-1. The expression levels of IGF-1 at mRNA and protein levels were remarkably downregulated. miR-511 significantly inhibited cell proliferation and promoted cell apoptosis by downregulating the phosphorylation level of AKT and ERK1/2. This finding confirmed that miR-511 inhibits proliferation and promotes apoptosis by downregulating the IGF-1 in PK-15 cells.

Keywords: Apoptosis; IGF-1; Proliferation; SNP; miR-511.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Binding Sites / genetics
  • Cell Line
  • Cell Proliferation / genetics*
  • Gene Expression Regulation / genetics
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • Kidney / cytology
  • Kidney / metabolism
  • Luciferases / genetics
  • MAP Kinase Signaling System / genetics
  • MicroRNAs / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Messenger / genetics
  • Swine
  • Transfection

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Luciferases
  • Proto-Oncogene Proteins c-akt