title: MiR-548c impairs migration and invasion of endometrial and ovarian cancer cells via downregulation of Twist.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a class of small non-coding RNAs, which post-transcriptionally repress the expression of genes involved in cancer initiation and progression. Although some miRNAs that target many signaling pathways (also called universe miRNAs) are supposed to play a global role in diverse human tumors, their regulatory functions in gynecological cancers remain largely unknown. We investigated the biological role and underlying mechanism of miR-548c (one universe miRNA) in endometrial and ovarian cancer.
  
  
  METHODS
  The effects of miR-548c overexpression on cell proliferation, migration and invasion were studied in endometrial and ovarian cancer cells. TWIST1 (Twist) was identified as a direct miR-548c target by western blot analysis and luciferase activity assay. The expression of miR-548c and Twist were examined by qRT-PCR in endometrial and ovarian cancer tissues.
  
  
  RESULTS
  Here, we report that miR-548c is down-regulated in endometrial and ovarian cancer tissues when compared to normal tissues, and our meta-analysis reveal that decreased miR-548c expression correlates with poor prognosis in endometrial cancer patients. We show that in endometrial and ovarian cancer cells, ectopic expression of miR-548c significantly inhibits whereas knockdown of miR-548c dramatically induces cancer cell proliferation, migration and invasion. By using luciferase reporter assay, we demonstrate that Twist, a known oncogene in endometrial and ovarian cancers, is a direct target of miR-548c. Furthermore, the expression of Twist partially abrogates the tumor suppressive effects of miR-548c on cell migration and invasion.
  
  
  CONCLUSIONS
  These findings suggest that miR-548c directly downregulates Twist, and provide a novel mechanism for Twist upregulation in both endometrial and ovarian cancers. The use of miR-548c may hold therapeutic potential for the treatment of Twist-overexpressing tumors.
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. xiaochunsun@hotmail.com.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, the Second Hospital of Jilin University, Changchun, 130041, China. cuimanhua@outlook.com.
authors.forename: Manhua
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. zhangaichen@outlook.jp.
authors.forename: Aichen
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. lingltong@sina.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. kun_wang2010@yahoo.co.jp.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. lkai792@yahoo.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. wangxue077@gmail.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. ziqiansun@yahoo.com.
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, 130021, China. zhang_hongyen@sina.com.
authors.forename: Hongye
authors.initials: H
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1