TY - JOUR
T1 - Decreased expression of microRNA-29 family in leiomyoma contributes to increased major fibrillar collagen production
AU - Marsh, Erica E.
AU - Steinberg, Marissa L.
AU - Parker, J. Brandon
AU - Wu, Ju
AU - Chakravarti, Debabrata
AU - Bulun, Serdar E.
N1 - Publisher Copyright:
© 2016 American Society for Reproductive Medicine
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Leiomyoma
KW - collagen
KW - extracellular matrix
KW - fibroids
KW - microRNA
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U2 - 10.1016/j.fertnstert.2016.05.001
DO - 10.1016/j.fertnstert.2016.05.001
M3 - Article
C2 - 27233758
AN - SCOPUS:84978492374
SN - 0015-0282
VL - 106
SP - 766
EP - 772
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 3
ER -