Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma

Although papillary thyroid carcinoma (PTC) displays strong heritability, no predisposing germ-line mutations have been found. We show that a common G/C polymorphism (rs2910164) within the pre-miR-146a sequence reduced the amount of pre- and mature miR-146a from the C allele 1.9- and 1.8-fold, respectively, compared with the G allele. This is matched by a similar decrease in the amount of each pre-miR generated from the corresponding pri-miR-146a in an in vitro processing reaction. The C allele also interfered with the binding of a nuclear factor to pre-miR-146a. The reduction in miR-146a led to less efficient inhibition of target genes involved in the Toll-like receptor and cytokine signaling pathway (TRAF6,…

• AT
  American Thyroid Association
• OS
  Ohio State University

  Awards: CA16058, P30 CA16058
• NC
  National Cancer Institute

  Awards: CA16058, P30 CA16058