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Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer

Leung, YK and Chan, QKY and Ng, CF and Ma, FMT and Tse, HM and To, KF and Maranchie, J and Ho, SM and Lau, KM (2014) Hsa-miRNA-765 as a key mediator for inhibiting growth, migration and invasion in fulvestrant-treated prostate cancer. PLoS ONE, 9 (5).

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Abstract

Fulvestrant (ICI-182,780) has recently been shown to effectively suppress prostate cancer cell growth in vitro and in vivo. But it is unclear whether microRNAs play a role in regulating oncogene expression in fulvestrant-treated prostate cancer. Here, this study reports hsa-miR-765 as the first fulvestrant-driven, ERβ-regulated miRNA exhibiting significant tumor suppressor activities like fulvestrant, against prostate cancer cell growth via blockage of cell-cycle progression at the G2/M transition, and cell migration and invasion possibly via reduction of filopodia/intense stress-fiber formation. Fulvestrant was shown to upregulate hsa-miR-765 expression through recruitment of ERβ to the 5′-regulatory-region of hsa-miR-765. HMGA1, an oncogenic protein in prostate cancer, was identified as a downstream target of hsa-miR-765 and fulvestrant in cell-based experiments and a clinical study. Both the antiestrogen and the hsa-miR-765 mimic suppressed HMGA1 protein expression. In a neo-adjuvant study, levels of hsa-miR-765 were increased and HMGA1 expression was almost completely lost in prostate cancer specimens from patients treated with a single dose (250 mg) of fulvestrant 28 days before prostatectomy. These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer. © 2014 Leung et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Leung, YK
Chan, QKY
Ng, CF
Ma, FMT
Tse, HM
To, KF
Maranchie, Jjkm26@pitt.eduJKM26
Ho, SM
Lau, KM
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorYu, JindanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 16 May 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0098037
Schools and Programs: School of Medicine > Urology
Refereed: Yes
Date Deposited: 30 Jun 2014 15:04
Last Modified: 26 Jan 2019 22:55
URI: http://d-scholarship.pitt.edu/id/eprint/22010

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