Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue

Liang Chen, Youhuai Li, Yebo Fu, Jin Peng, Meng Hsuan Mo, Michael Stamatakos, Christine B. Teal, Rachel F. Brem, Alexander Stojadinovic, Michael Grinkemeyer, Timothy A. McCaffrey, Yan Gao Man, Sidney W. Fu

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-β pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.

Original languageEnglish (US)
Article numbere54213
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 29 2013
Externally publishedYes

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Carcinoma, Intraductal, Noninfiltrating
MicroRNAs
microRNA
formalin
breast neoplasms
Paraffin
alkanes
Formaldehyde
carcinoma
Tissue
Breast Neoplasms
hyperplasia
Ductal Carcinoma
Deregulation
breasts
Breast
Microdissection
tissues
Messenger RNA
Molecules

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chen, L., Li, Y., Fu, Y., Peng, J., Mo, M. H., Stamatakos, M., ... Fu, S. W. (2013). Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue. PLoS One, 8(1), [e54213]. https://doi.org/10.1371/journal.pone.0054213

Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue. / Chen, Liang; Li, Youhuai; Fu, Yebo; Peng, Jin; Mo, Meng Hsuan; Stamatakos, Michael; Teal, Christine B.; Brem, Rachel F.; Stojadinovic, Alexander; Grinkemeyer, Michael; McCaffrey, Timothy A.; Man, Yan Gao; Fu, Sidney W.

In: PLoS One, Vol. 8, No. 1, e54213, 29.01.2013.

Research output: Contribution to journalArticle

Chen, L, Li, Y, Fu, Y, Peng, J, Mo, MH, Stamatakos, M, Teal, CB, Brem, RF, Stojadinovic, A, Grinkemeyer, M, McCaffrey, TA, Man, YG & Fu, SW 2013, 'Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue', PLoS One, vol. 8, no. 1, e54213. https://doi.org/10.1371/journal.pone.0054213
Chen, Liang ; Li, Youhuai ; Fu, Yebo ; Peng, Jin ; Mo, Meng Hsuan ; Stamatakos, Michael ; Teal, Christine B. ; Brem, Rachel F. ; Stojadinovic, Alexander ; Grinkemeyer, Michael ; McCaffrey, Timothy A. ; Man, Yan Gao ; Fu, Sidney W. / Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue. In: PLoS One. 2013 ; Vol. 8, No. 1.
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