MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer

Fateen Farhana Ibrahim, A. Rahman A. Jamal, Saiful Effendi Syafruddin, Nurul Syakima Ab Mutalib, Sazuita Saidin, Reena Rahayu Md Zain, Mohammad Manir Hossain Mollah, Norfilza Mohd Mokhtar

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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.

Original languageEnglish
Article number56
JournalJournal of Ovarian Research
Volume8
Issue number1
DOIs
Publication statusPublished - 12 Aug 2015

Fingerprint

MicroRNAs
Ovarian Neoplasms
Cell Proliferation
Cell Movement
In Situ Hybridization
Ovarian epithelial cancer
Neoplasm Genes
Liver Neoplasms
Genes
Disease Progression
Real-Time Polymerase Chain Reaction
Cell Survival
Down-Regulation
Neoplasm Metastasis
Gene Expression
Cell Line

Keywords

  • In situ hybridization
  • Invasion
  • MicroRNA
  • Migration
  • miR-200c
  • miR-31
  • Serous ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

@article{2f804fc926f14173b62ba3bdea717cce,
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.",
keywords = "In situ hybridization, Invasion, MicroRNA, Migration, miR-200c, miR-31, Serous ovarian cancer",
author = "Ibrahim, {Fateen Farhana} and {A. Jamal}, {A. Rahman} and Syafruddin, {Saiful Effendi} and {Ab Mutalib}, {Nurul Syakima} and Sazuita Saidin and {Md Zain}, {Reena Rahayu} and {Hossain Mollah}, {Mohammad Manir} and {Mohd Mokhtar}, Norfilza",
year = "2015",
month = "8",
day = "12",
doi = "10.1186/s13048-015-0186-7",
language = "English",
volume = "8",
journal = "Journal of Ovarian Research",
issn = "1757-2215",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer

AU - Ibrahim, Fateen Farhana

AU - A. Jamal, A. Rahman

AU - Syafruddin, Saiful Effendi

AU - Ab Mutalib, Nurul Syakima

AU - Saidin, Sazuita

AU - Md Zain, Reena Rahayu

AU - Hossain Mollah, Mohammad Manir

AU - Mohd Mokhtar, Norfilza

PY - 2015/8/12

Y1 - 2015/8/12

N2 - 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.

AB - 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.

KW - In situ hybridization

KW - Invasion

KW - MicroRNA

KW - Migration

KW - miR-200c

KW - miR-31

KW - Serous ovarian cancer

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U2 - 10.1186/s13048-015-0186-7

DO - 10.1186/s13048-015-0186-7

M3 - Article

C2 - 26260454

AN - SCOPUS:84938864883

VL - 8

JO - Journal of Ovarian Research

JF - Journal of Ovarian Research

SN - 1757-2215

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