A polymorphism in a let‐7 microRNA binding site of KRAS in women with endometriosis
Open accessAbstract
Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk.
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A mutation that commonly leads to endometriosis has not been identified.
“Although multiple candidate genes have been postulated, a mutation that commonly leads to endometriosis has not been identified.14,15”
From Altered genome-wide methylation in endometriosis (2014) · cites this paper as [15]
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- Authors
- Grechukhina, O., Petracco, R., Popkhadze, S., Massasa, E., Paranjape, T., Chan, E., Flores, I., Weidhaas, J. B., & Taylor, H. S.
- Affiliations
- Yale University (US)
- Ponce Health Sciences University (PR)
- Corresponding author
- Weidhaas, Joanne B.
- Taylor, Hugh S.
- Venue
- EMBO Molecular Medicine
- Published
- 2012-02-03
- Volume
- 4
- Issue
- 3
- Pages
- 206-217
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC3376847
- OpenAlex
- W2165596244
- Cited by
- 96
- References
- 49
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 17 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 7
- FWCI
- 12.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (U54 HD052668, R01 HD036887)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Plant and fungal interactions
- Keywords
- endometriosis, KRAS, let-7 microRNA, microRNA binding sites, 3'UTR polymorphism, endometrial stromal cells, cell proliferation, cell invasion, progesterone receptor, genetic susceptibility markers
- MeSH terms
- Adult, Alleles, Animals, Binding Sites, Endometriosis, Female, Humans, Mutation, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Mice, SCID, Stromal Cells, ras Proteins, Polymorphism, Single Nucleotide, MicroRNAs, Mice, Young Adult
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