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.
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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