MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer.

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MARC

Aydoğdu, Eylem (author)

MicroRNA-regulated gene networks during mammary cell differentiation are associated with breast cancer.

Article/chapterEnglish2012

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2012-05-04
Oxford University Press (OUP),2012
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LIBRIS-ID:oai:DiVA.org:kth-165356
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-165356URI
https://doi.org/10.1093/carcin/bgs161DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:125121010URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

QC 20150505
MicroRNAs (miRNAs) play pivotal roles in stem cell biology, differentiation and oncogenesis and are of high interest as potential breast cancer therapeutics. However, their expression and function during normal mammary differentiation and in breast cancer remain to be elucidated. In order to identify which miRNAs are involved in mammary differentiation, we thoroughly investigated miRNA expression during functional differentiation of undifferentiated, stem cell-like, murine mammary cells using two different large-scale approaches followed by qPCR. Significant changes in expression of 21 miRNAs were observed in repeated rounds of mammary cell differentiation. The majority, including the miR-200 family and known tumor suppressor miRNAs, was upregulated during differentiation. Only four miRNAs, including oncomiR miR-17, were downregulated. Pathway analysis indicated complex interactions between regulated miRNA clusters and major pathways involved in differentiation, proliferation and stem cell maintenance. Comparisons with human breast cancer tumors showed the gene profile from the undifferentiated, stem-like stage clustered with that of poor-prognosis breast cancer. A common nominator in these groups was the E2F pathway, which was overrepresented among genes targeted by the differentiation-induced miRNAs. A subset of miRNAs could further discriminate between human non-cancer and breast cancer cell lines, and miR-200a/miR-200b, miR-146b and miR-148a were specifically downregulated in triple-negative breast cancer cells. We show that miR-200a/miR-200b can inhibit epithelial-mesenchymal transition (EMT)-characteristic morphological changes in undifferentiated, non-tumorigenic mammary cells. Our studies propose EphA2 as a novel and important target gene for miR-200a. In conclusion, we present evidentiary data on how miRNAs are involved in mammary cell differentiation and indicate their related roles in breast cancer.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
SRA - Molecular Bioscience
SRA - Molekylär biovetenskap

Added entries (persons, corporate bodies, meetings, titles ...)

Katchy, Anne (author)
Tsouko, Efrosini (author)
Lin, Chin-Yo (author)
Haldosén, Lars-ArneKarolinska Institutet (author)
Helguero, Luisa (author)
Williams, Cecilia,1969-University of Houston(Swepub:kth)u1ygqmuy (author)
Karolinska InstitutetUniversity of Houston (creator_code:org_t)

Related titles

In:Carcinogenesis: Oxford University Press (OUP)33:8, s. 1502-110143-33341460-2180

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By the author/editor: Aydoğdu, Eylem; Katchy, Anne; Tsouko, Efrosini; Lin, Chin-Yo; Haldosén, Lars-A ...; Helguero, Luisa; show more...; Williams, Cecili ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Articles in the publication: Carcinogenesis

By the university: Royal Institute of Technology; Karolinska Institutet

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