title: MicroRNA-106b is involved in transforming growth factor β1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma.
abstract: BACKGROUND
  MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor β1(TGF-β1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-β1-involvement in the tumorigenesis of cervical cancer remain unknown.
  
  
  METHODS
  The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-β1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene.
  
  
  RESULTS
  miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-β facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-β1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-β1 partly through miR-106b and was involved in TGF-β1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay.
  
  
  CONCLUSIONS
  Our data suggest that the TGF-β1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma.
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China. chengyuan@bjmu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China. yanliguo121@sina.com.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovasicular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. zhangyy@bjmu.edu.cn.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China. youketg@163.com.
authors.forename: Ke
authors.initials: K
authors.lastname: You
authors.affiliation: Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Cardiovasicular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, 100191, China. lizijian@bjmu.edu.cn.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China. gengli1957@bjmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Geng
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins