Decreased expression of microRNA-29 family in leiomyoma contributes to increased major fibrillar collagen production

The microRNA-29 family is down-regulated in leiomyoma versus myometrium. This down-regulation leads to collagen overexpression in leiomyoma and can be reversed by overexpressing microRNA-29 in leiomyoma cells.

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Volume 106, Issue 3, Pages 766-772

Authors:

Erica E. Marsh, M.D., M.S.C.I., Marissa L. Steinberg, M.D., J. Brandon Parker, Ph.D., Ju Wu, M.D., Debabrata Chakravarti, Ph.D., Serdar E. Bulun, M.D.

Abstract:

Objective

To determine the expression and function of the microRNA-29 family (miRNA-29a, miRNA-29b, miRNA-29c) in human leiomyoma and myometrium.

Design

Basic science experimental design.

Setting

Academic medical center.

Patient(s)

Women undergoing surgery for symptomatic uterine fibroids.

Intervention(s)

Overexpression and knockdown of miRNA-29a, miRNA-29b, and miRNA-29c in primary leiomyoma and myometrial cells.

Main Outcome Measure(s)

[1] Expression of the miRNA-29 family members in vivo in leiomyoma versus myometrium; [2] Major fibrillar collagen (I, II, III) expression in leiomyoma and myometrial cells with manipulation of miRNA-29 species.

Result(s)

Members of the miRNA-29 family (29a, 29b, 29c) are all down-regulated in leiomyoma versus myometrium in vivo. The expression of the miRNA-29 family can be successfully modulated in primary leiomyoma and myometrial cells. Overexpression of the miRNA-29 family in leiomyoma cells results in down-regulation of the major fibrillar collagens. Down-regulation of the miRNA-29 species in myometrium results in an increase in collagen type III deposition.

Conclusion(s)

The miRNA-29 family is consistently down-regulated in leiomyoma compared to matched myometrial tissue. This down-regulation contributes to the increased collagen seen in leiomyomas versus myometrium. When miRNA-29 members are overexpressed in leiomyoma cells, protein levels of all of the major fibrillar collagens decrease. The miRNA-29 members are potential therapeutic targets in this highly prevalent condition.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility┬« is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.