Research Repository

miR-204 is dysregulated in metastatic prostate cancer in vitro

Todorova, Krassimira and Metodiev, Metodi V and Metodieva, Gergana and Zasheva, Diana and Mincheff, Milcho and Hayrabedyan, Soren (2016) 'miR-204 is dysregulated in metastatic prostate cancer in vitro.' Molecular Carcinogenesis, 55 (2). pp. 131-147. ISSN 0899-1987

Full text not available from this repository.


During cancer progression, the genome instability incurred rearrangement could possibly turn some of the tumor suppressor micro-RNAs into pro-oncogenic ones. We aimed to investigate miR-204 in the context of prostate cancer progression using a cell line model of different levels of genome instability (LNCaP, PC3, VCaP and NCI H660), as demonstrated by the availability of ERG fusion. We studied the effect of miR-204 modulation on master transcription factors important for lineage development, cell differentiation and prostate cancer bone marrow metastasis. We followed c-MYB, ETS1 and RUNX2 transcript and protein expression and the miR-204 affected global proteome. We further investigated if these transcription factors exert an effect on miR-204 expression (qPCR, luciferase reporter assay) by silencing them using esiRNA. We found dualistic miR-204 effects, either acting as a tumor suppressor on c-MYB, or as an oncomiR on ETS1. RUNX2 and ETS1 regulation by miR-204 was ERG fusion dependent, demonstrating regulatory circuitry disruption in advanced metastatic models. miR-204 also differentially affected mRNA splicing and protein stability. miR-204 levels were found dependent on cancer hypermethylation and supported by positive feedback induced by all three transcription factors. In this regulatory circuitry among miR-204, c-MYB, RUNX2 and ETS1, the c-MYB was found to induce all three other members, but its expression was differentially affected by the methylation status in lymph node vs. bone metastasis. We demonstrate that not only tumor suppressor micro-RNA loss, but also significant genome rearrangement-driven regulatory loop perturbations play a role in the advanced cancer progression, conferring better pro-survival and metastatic potential.

Item Type: Article
Uncontrolled Keywords: (MeSH); Micro RNA; Transcription Factor; Oncogene Fusion; DNA Methylation; LTQ Orbitrap Velos Proteomics
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 10 Feb 2015 18:46
Last Modified: 23 Sep 2022 18:47

Actions (login required)

View Item View Item