title: MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer.
abstract: BACKGROUND
  Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells.
  
  
  METHODS
  Twenty-two SEOC and twenty-two normal samples were subjected to miRNA expression profiling using the locked nucleic acid (LNA) quantitative real-time PCR (qPCR). The localization of miR-200c was determined via LNA in situ hybridization (ISH). Functional analysis of miR-200c and miR-31 on cell proliferation, migration and invasion and clonogenic cell survival were assessed in vitro. The putative target genes of the two miRNAs were predicted by miRWalk program and expression of the target genes in SEOC cell lines was validated.
  
  
  RESULTS
  The miRNA expression profiling revealed thirty-eight significantly dysregulated miRNAs in SEOC compared to normal ovarian tissues. Of these, eighteen were up-regulated whilst twenty miRNAs were down-regulated. We observed chromogenic miR-200c-ISH signal predominantly in the cytoplasmic compartment of both epithelial and inflammatory cancer cells. Re-expression of miR-200c significantly increased the cell proliferation and colony formation but reduced the migration and invasion of SEOC cells. In addition, miR-200c expression was inversely proportionate with the expression of deleted in liver cancer-1 (DLC-1) gene. Over-expression of miR-31 in SEOC cells resulted in decreased cell proliferation, clonogenic potential, cell migration and invasion. Meanwhile, miR-31 gain-of-function led to the down-regulation of AF4/FMR2 family member 1 (AFF1) gene.
  
  
  CONCLUSIONS
  These data suggested that miR-200c and miR-31 may play roles in the SEOC metastasis biology and could be considered as promising targets for therapeutic purposes.
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. fateeniasani@gmail.com.
authors.forename: Fateen Farhana
authors.initials: FF
authors.lastname: Ibrahim
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. rahmanj@ppukm.ukm.edu.my.
authors.forename: Rahman
authors.initials: R
authors.lastname: Jamal
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. effendisy@ppukm.ukm.edu.my.
authors.forename: Saiful Effendi
authors.initials: SE
authors.lastname: Syafruddin
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. nurulsyakima@gmail.com.
authors.forename: Nurul Syakima
authors.initials: NS
authors.lastname: Ab Mutalib
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. sazuita@yahoo.com.
authors.forename: Sazuita
authors.initials: S
authors.lastname: Saidin
authors.affiliation: Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia. ayureena@hotmail.com.
authors.forename: Reena Rahayu
authors.initials: RR
authors.lastname: MdZin
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. mhmollah06@yahoo.com.
authors.forename: Mohammad Manir
authors.initials: MM
authors.lastname: Hossain Mollah
authors.affiliation: UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. norfilza@ppukm.ukm.edu.my.|Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. norfilza@ppukm.ukm.edu.my.
authors.forename: Norfilza Mohd
authors.initials: NM
authors.lastname: Mokhtar
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008296:Malaysia; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012704:Serous Membrane / Q000473:pathology
chemical_list: C533896:MIRN200 microRNA, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs