Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming
2024

How a specific kinase affects uterine fibroids

publication

Author Information

Author(s): Khadka Subash, Lukas Brandon, Sun Claire Xin, Muralimanoharan Sribalasubashini, Shanmugasundaram Karthigayan, Khosh Azad, Schenken Claire, Stansbury Nicholas, Schenken Robert, Firestein Ron, Dai Yang, Boyer Thomas

Hypothesis

Pharmacologic inhibition of CDK8/19 in myometrial stem cells will trigger their differentiation into tumor initiating cells characteristic of uterine fibroids.

Conclusion

Inhibiting CDK8/19 in myometrial stem cells leads to changes that promote the development of uterine fibroids.

Supporting Evidence

  • Uterine fibroids are the most common non-cutaneous tumors in women worldwide.
  • Mutations in the RNA polymerase II Mediator subunit MED12 are dominant drivers of uterine fibroids.
  • Inhibition of CDK8/19 removes a barrier to myogenic differentiation in myometrial stem cells.

Takeaway

Scientists found that blocking a certain protein in stem cells can help them turn into cells that cause uterine fibroids, which are common tumors in women.

Methodology

Pharmacologic inhibition of CDK8/19 was used to study its effects on myometrial stem cells.

Digital Object Identifier (DOI)

10.21203/rs.3.rs-5125876

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