title: Down-regulation of miR-29b is essential for pathogenesis of uterine leiomyoma.
abstract: Uterine leiomyomata (LMs) are the most common tumor affecting the female reproductive organs. The most notable pathophysiologic feature of this tumor is the excessive accumulation of rigid extracellular matrix (ECM) composed mainly of collagen types I and III. It is believed that the rigidity of the collagen-rich ECM causes symptoms such as abnormal bleeding and pelvic pain/pressure. However, the molecular pathogenesis for this ECM-rich tumor has yet to be elucidated. We have established that miR-29b was consistently down-regulated in LM compared with myometrium (MM). Hence, the function of miR-29b in LM was examined in vivo using adult female ovariectomized NOD-scid IL2Rγ(null) mice for subrenal xenograft models. In LM xenografts, restoring miR-29b inhibited the accumulation of ECM and the development of solid tumors. Although the miR-29b knockdown in MM cells increased the expression of collagens, it did not transform MM cells into tumorigenic, indicating that the down-regulation of miR-29b is essential but not sufficient for LM tumorigenesis. In addition, 17β-estradiol and progesterone down-regulated miR-29b and up-regulated mRNAs for multiple collagens in LM xenografts. Thus, we conclude that ECM production in LMs is regulated by steroid hormones via down-regulation of miR-29b, which is one of the mechanisms underlying the excessive accumulation of ECM.
authors.affiliation: Division of Reproductive Science in Medicine (W.Q., V.A.S., S.A.D., Y.L., M.E.-F., T.K.), Department of Obstetrics and Gynecology, Center of Genetic Medicine; Department of Pathology (Z.L., J.J.W.); Robert H. Lurie Comprehensive Cancer Center (W.Q., J.J.W., T.K.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.
authors.forename: Wenan
authors.initials: W
authors.lastname: Qiang
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.forename: Vanida Ann
authors.initials: VA
authors.lastname: Serna
authors.forename: Stacy Ann
authors.initials: SA
authors.lastname: Druschitz
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Margarita
authors.initials: M
authors.lastname: Espona-Fiedler
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurita
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009368:Neoplasm Transplantation; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D003094:Collagen