mir-200

microRNAs mediate uterine contraction during pregnancy and labor

by Chris on November 22, 2010

miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor

Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, whereas spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and have a negative impact on PR function. In this study, we uncovered a previously undescribed regulatory pathway whereby micro-RNAs (miRNAs) serve as hormonally modulated and conserved mediators of contraction-associated genes in the pregnant uterus in the mouse and human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans as well as two coordinately down-regulated targets, zinc finger E-box binding homeobox proteins ZEB1 and ZEB2, which act as transcriptional repressors. We also observed up-regulation of the miR-200 family and down-regulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly up-regulated by the action of progesterone (P4)/PR at the ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibit expression of the contraction-associated genes, oxytocin receptor and connexin-43, and block oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets, ZEB1 and ZEB2, as unique P4/PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor and shed light on the molecular mechanisms involved in preterm birth.

Renthal, N. E. et al. (2010) miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor. Proc Natl Acad Sci USA [Epub ahead of print]. [abstract]

Reviews of this important article…

MicroRNAs mediate an early birth
Nature.com – Joseph Milton - ‎Nov 16, 2010‎
“This miRNA family is highly conserved between mice and humans and the mechanism also appears to be conserved,” explains Mendelson. Mendelson says that many …

RNA-based drugs may prevent premature labour
Oneindia - ‎Nov 16, 2010‎
Washington, Nov 16 (ANI): Researchers at UT Southwestern Medical Center have discovered in a preclinical study that tiny molecules called microRNAs act …

RNA-based medications may prevent premature labour
TopNews - Piyush Diwan - ‎Nov 17, 2010‎
A new research has found that microRNA’s interact with hormones to prevent the risk of premature labor. Researchers looked at pregnant mice, and found that …

MicroRNA molecules apparently control labor
HealthJockey.com - ‎Nov 16, 2010‎
Tiny microRNA molecules known for their involvement in most biologic processes seem to play a mighty role while managing labor. …

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microRNA of the Week: microRNA-200 Family

by Chris on March 26, 2010

The miR-200 family is a particularly nasty group of microRNAs. Changes in miR-200 family levels have been associated with enhanced tumorigenesis and significantly correlated with decreased survival. 

miR-200 family members are associated with resistance to several chemotherapy drugs: docetaxel  in non-small cell cancer cells1, cisplatin in breast cancer cells2, and gemcitabine in cholangiocarcinoma cells.

It has been shown that many microRNAs play an important role in regulating metastasis, the ultimate cause of death of most cancer patients, and in particular, miR-200 is responsible for direct enhancement of distant metastases of breast cancer3.

Additionally miR-200 family members are significantly over-expressed in human ovarian cancer4 and likewise are a factor in the etiology of endometriosis5.

  1. Rui W, Bing F, Hai-Zhu S, Wei D, Long-Bang C.  (2009)  Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).  J Cell Mol Med [Epub ahead of print]  [abstract]
  2. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer [Epub ahead of print] [abstract]
  3. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J.  (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastases.  PLoS One 4(9), e7181.  [abstract]
  4. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Ménard S, Croce CM. (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18), 8699-707. [abstract]
  5. Filigheddu N, Gregnanin I, Porporato PE, Surico D, Perego B, Galli L, Patrignani C, Graziani A, Surico N. Differential expression of microRNAs between eutopic and ectopic endometrium in ovarian endometriosis. J Biomed Biotechnol 2010:369549. [abstract]

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