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

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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