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J Ovarian Res. 2015 Aug 12;8:56. doi: 10.1186/s13048-015-0186-7.

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

Author information

1
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. fateeniasani@gmail.com.
2
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.
3
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.
4
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. nurulsyakima@gmail.com.
5
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. sazuita@yahoo.com.
6
Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia. ayureena@hotmail.com.
7
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Jalan Yaa'cob Latiff, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia. mhmollah06@yahoo.com.
8
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.
9
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.

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.

PMID:
26260454
PMCID:
PMC4531514
DOI:
10.1186/s13048-015-0186-7
[Indexed for MEDLINE]
Free PMC Article
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