Unknown

Dataset Information

0

A common single-nucleotide polymorphism in cyclooxygenase-2 disrupts microRNA-mediated regulation.


ABSTRACT: Elevated expression of the prostaglandin synthase cyclooxygenase-2 (COX-2) is commonly observed in many chronic inflammatory diseases and cancer. However, the mechanisms allowing for pathogenic COX-2 overexpression are largely unknown. The gene for COX-2 (PTGS2) carries a common single-nucleotide polymorphism (SNP) at position 8473 (T8473C), in exon 10 that is associated with diseases in which COX-2 overexpression is a contributing factor. We demonstrate that the T8473C SNP resides within a region that targets COX-2 mRNA for degradation through microRNA-mediated regulation. miR-542-3p was identified to bind transcripts derived from the 8473T allele and promote mRNA decay. By contrast, the presence of the variant 8473C allele interfered with miR-542-3p binding, allowing for mRNA stabilization, and this effect was rescued using a mutated miR-542-3p at the respective 8473 site. Colon cancer cells and tissue displayed COX-2 mRNA levels that were dependent on T8473C allele dosage, and allele-specific expression of COX-2 was observed to be a contributing factor promoting COX-2 overexpression. These findings provide a novel molecular explanation underlying disease susceptibility associated with COX-2 T8473C SNP, and identify it as a potential marker for identifying cancer patients best served through selective COX-2 inhibition.

SUBMITTER: Moore AE 

PROVIDER: S-EPMC3454533 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

A common single-nucleotide polymorphism in cyclooxygenase-2 disrupts microRNA-mediated regulation.

Moore A E AE   Young L E LE   Dixon D A DA  

Oncogene 20110808 12


Elevated expression of the prostaglandin synthase cyclooxygenase-2 (COX-2) is commonly observed in many chronic inflammatory diseases and cancer. However, the mechanisms allowing for pathogenic COX-2 overexpression are largely unknown. The gene for COX-2 (PTGS2) carries a common single-nucleotide polymorphism (SNP) at position 8473 (T8473C), in exon 10 that is associated with diseases in which COX-2 overexpression is a contributing factor. We demonstrate that the T8473C SNP resides within a regi  ...[more]

Similar Datasets

| S-EPMC5418741 | biostudies-literature
| S-EPMC2230662 | biostudies-literature
| 2135070 | ecrin-mdr-crc
| S-EPMC2664626 | biostudies-literature
| S-EPMC10684809 | biostudies-literature
| S-EPMC1986627 | biostudies-literature
| S-EPMC4165621 | biostudies-literature
| S-EPMC5582881 | biostudies-literature
| S-EPMC3464600 | biostudies-literature
| S-EPMC4198472 | biostudies-literature