Three functional polymorphisms in CCDC170 were associated with osteoporosis phenotype

Biol Open. 2021 Apr 15;10(4):bio050930. doi: 10.1242/bio.050930. Epub 2021 Apr 16.

Abstract

MicroRNAs (miRNAs) play essential roles in regulating bone formation and homeostasis. Genomic variations within miRNA target sites may therefore be important sources of genetic differences in osteoporosis risk. The function of CCDC170 in bone biology is still unclear. To verify the function of CCDC170, we knocked down CCDC170 in cells and mice and searched for miRNA recognition sites within CCDC170 using the TargetScan, miRNASNP, and miRBase databases. In this study, our results demonstrated that CCDC170 plays an important role in the positive regulation of bone formation. MiR-153-3p, miR-374b-3p, miR-4274, miR-572 and miR-2964a-5p inhibited CCDC170 expression in an allele-specific manner by binding GWAS lead SNPs rs6932603, rs3757322 and rs3734806. These findings may improve our understanding of the association between CCDC170, miRNAs, GWAS lead SNPs, and osteoporosis pathogenesis and may provide a potential therapeutic target for osteoporosis therapy.

Keywords: CCDC170; GWAS lead SNP; Osteoporosis risk; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Alleles*
  • Animals
  • Biomarkers
  • Carrier Proteins / genetics*
  • Cell Line
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Mice
  • MicroRNAs / genetics
  • Osteogenesis / genetics
  • Osteoporosis / diagnosis*
  • Osteoporosis / etiology*
  • Polymorphism, Single Nucleotide*
  • RNA Interference
  • X-Ray Microtomography

Substances

  • 3' Untranslated Regions
  • Biomarkers
  • CCDC170 protein, human
  • Carrier Proteins
  • MicroRNAs