Decreased expression of microRNA 29 family in leiomyoma contributes to increased major fibrillar collagen production
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.
To determine the expression and function of the microRNA-29 family (miRNA-29a, miRNA-29b, miRNA-29c) in human leiomyoma and myometrium.
Basic science experimental design.
Academic medical center.
Women undergoing surgery for symptomatic uterine fibroids.
Overexpression and knockdown of miRNA-29a, miRNA-29b, and miRNA-29c in primary leiomyoma and myometrial cells.
Main Outcome Measure(s):
 Expression of the miRNA-29 family members in vivo in leiomyoma versus myometrium;  Major fibrillar collagen (I, II, III) expression in leiomyoma and myometrial cells with manipulation of miRNA-29 species.
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.
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.