Abstract

DNAJB6 is a constitutively expressed member of the HSP40 family. It has been described as a negative regulator of breast tumor progression and a regulator of epithelial phenotype. Expression of DNAJB6 is reported to be compromised with tumor progression. However, factors responsible for its downregulation are still undefined. We used a knowledge-based screen for identifying miRNAs capable of targeting DNAJB6. In this work, we present our findings that hsa-miR-632 (miR-632) targets the coding region of DNAJB6. Invasive and metastatic breast cancer cells express high levels of miR-632 compared with mammary epithelial cells. Analysis of RNA from breast tumor specimens reveals inverse expression patterns of DNAJB6 transcript and miR-632. In response to exogenous miR-632 expression, DNAJB6 protein levels are downregulated and the resultant cell population shows significantly increased invasive ability. Silencing endogenous miR-632 abrogates invasive ability of breast cancer cells and promotes epithelial like characteristics noted by E-cadherin expression with concomitant decrease in mesenchymal markers such as Zeb2 and Slug. Thus, miR-632 is a potentially important epigenetic regulator of DNAJB6, which contributes to the downregulation of DNAJB6 and plays a supportive role in malignant progression.

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Publisher Full Text

Authors

Mitra A, Rostas JW, Dyess DL, Shevde LA, Samant RS

Institution

Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Spring Hill Avenue, Mobile, AL 36604, USA.

Source

Laboratory investigation; a journal of technical methods and pathology 92:9 2012 Sep pg 1310-7

MeSH

Base Sequence
Binding Sites
Blotting, Western
Breast Neoplasms
DNA Primers
Down-Regulation
Female
HSP40 Heat-Shock Proteins
Humans
MicroRNAs
Molecular Chaperones
Nerve Tissue Proteins
Reverse Transcriptase Polymerase Chain Reaction

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22710984