MicroRNA miR-30 family regulates non-attachment growth of breast cancer cellsReportar como inadecuado




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BMC Genomics

, 14:139

Human and rodent genomics

Abstract

BackgroundA subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells BT-ICs may open the road for novel therapeutic strategies. As microRNAs miRNAs control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions.

ResultsWe found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression.

ConclusionsmiR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs.

KeywordsBreast cancer BT-ICs Mammospheres microRNAs miR-30 family AVEN AbbreviationsAVENApoptosis, caspase activation inhibitor

BT-ICsBreast tumor initiating cells

FOXD1Forkhead box protein 1

FDRFalse discovery rate

KDKnock-down

miRmicroRNA

qRT-PCRQuantitative reverse transcription-polymerase chain reaction

s.c.Subcutaneous

UTRUnstranslated region

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-14-139 contains supplementary material, which is available to authorized users.

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Autor: Maria Ouzounova - Tri Vuong - Pierre-Benoit Ancey - Mylène Ferrand - Geoffroy Durand - Florence Le-Calvez Kelm - Carlo Cro

Fuente: https://link.springer.com/



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