Abstract:
BACKGROUND:Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. RESULTS:MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. CONCLUSIONS:A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Costa-Pinheiro P,Ramalho-Carvalho J,Vieira FQ,Torres-Ferreira J,Oliveira J,Gonçalves CS,Costa BM,Henrique R,Jerónimo Cdoi
10.1186/s13148-015-0076-2subject
Has Abstractpub_date
2015-04-10 00:00:00pages
42eissn
1868-7075issn
1868-7083pii
76journal_volume
7pub_type
杂志文章abstract:BACKGROUND:The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in vivo.Genome-wide DNA methylation was assessed using a MeDIP-chip analysis. All methylated DNA immunoprecipit...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-6-1
更新日期:2014-01-02 00:00:00
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doi:10.1186/s13148-015-0109-x
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journal_title:Clinical epigenetics
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journal_title:Clinical epigenetics
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doi:10.1186/s13148-018-0501-4
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journal_title:Clinical epigenetics
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doi:10.1186/s13148-014-0032-6
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pub_type: 已发布勘误
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pub_type: 杂志文章
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journal_title:Clinical epigenetics
pub_type: 杂志文章,多中心研究
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0029-3
更新日期:2011-08-01 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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doi:10.1186/s13148-020-00880-y
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journal_title:Clinical epigenetics
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journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
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更新日期:2019-03-15 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1007/s13148-011-0038-2
更新日期:2011-08-01 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2017-01-13 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0122-0
更新日期:2015-08-21 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2015-03-31 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2015-03-29 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
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更新日期:2020-09-11 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0040-6
更新日期:2015-01-22 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0172-y
更新日期:2016-01-20 00:00:00
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journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00