BMPR1B up-regulation via a miRNA binding site variation defines endometriosis susceptibility and CA125 levels

PloS One
Cherry Yin-Yi ChangFuu-Jen Tsai

Abstract

Bone morphogenetic protein receptor I B (BMPR1B) is a transmembrane receptor mediating TGF-β signal transduction. Recent studies indicate a tumor suppressor role for BMPR1B in ovarian cancer. Polymorphism at BMPR1B 3'UTR within the miR-125b binding site alters its binding affinity toward the miRNA, which may result in insufficient post-transcriptional repression. Single-nucleotide polymorphisms rs1970801, rs1434536, and rs11097457 near the miR-125b binding site in BMPR1B were genotyped by Taqman assay on 193 endometriosis patients and 202 healthy controls. BMPR1B and CA125 levels in ectopic endometrial tissues were evaluated by quantitative PCR and immunohistochemistry. Luciferase reporter assay was utilized to verify regulatory roles of BMPR1B 3'UTR with allelic variants of rs1434536 in a cell line model. Cell proliferation and migration were recorded, while expression of BMPR1B, CA125, glucocorticoid receptor (GCCR) and IL-1β were measured by quantitative PCR in endometrial cells transfected with wild-type or mutated miR-125b. This study found two endometriosis-associated SNPs, rs1434536 (P = 0.010) and rs1970801 (P = 0.0087), located within and next to a miR-125b binding site on BMPR1B. Interestingly, patients with homozygou...Continue Reading

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Citations

Jan 3, 2016·Bone·Neha S Dole, Anne M Delany
Feb 6, 2019·Biology of Reproduction·Sarah Bjorkman, Hugh S Taylor
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Aug 3, 2016·Cold Spring Harbor Perspectives in Biology·Carl-Henrik Heldin, Aristidis Moustakas

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Methods Mentioned

BETA
genotyping
PCR
biopsy
transfection
flow-cytometry
Assay
reverse transcription PCR
fluorescence-activated cell sorting

Software Mentioned

JLIN
SPSS
R

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