Micro-RNA-632 downregulates DNAJB6 in breast cancer.
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.
Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, 1660 Spring Hill Avenue, Mobile, AL 36604, USA.
Aparna
A
Mitra
Jack W
JW
Rostas
Donna L
DL
Dyess
Lalita A
LA
Shevde
Rajeev S
RS
Samant
D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D018832:Molecular Chaperones / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; C576158:MIRN632 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins