▶Subject: A powerful oncogenic miRNA controlling hallmarks of cancer

▶Speaker: Su Jung Song, Ph.D.

(Cancer Genetics Program, Beth Israel Deaconess Medical Center, Harvard Medical School)
 

▶Date: 2:00PM/February/18(Tue)/2014

 

▶Place: Life Science Bldg. #104

  *Abctract
MicroRNAs (miRNAs), a new class of regulatory genes, function in multiple cellular processes, including proliferation, differentiation and apoptosis, and a deregulation of miRNAs is commonly associated with human diseases. Metastasis is a hallmark of cancer that is resistant to conventional therapies. Genetic and epigenetic instability as well as the ability of self-renewal of cancer cells allow the malignant cells to escape from the primary tumor and colonize into the secondary site. The discovery of the contribution of epigenetic alterations to cancer has been of enormous importance. Hence, it is tempting to speculate that epigenetic mechanisms regulate the miRNA genes that are involved in the pathogenesis of cancer metastasis. Using the tissue-specific transgenic mouse models, we find that miR-22 triggers epithelial-mesenchymal transition (EMT), enhances stemness and promotes breast cancer development and metastasis. Notably, miR-22 exerts its metastatic potential by antagonizing anti-metastatic miR-200 through targeting the TET methylcytosine dioxygenase family members. Furthermore, high expression of miR-22 has been found to correlate with poor clinical outcomes and silencing of the TET-miR-200 axis in human breast cancer patients. Furthermore, we demonstrate that miR-22 reduces the global level of 5-hydroxymethylcytosine (5-hmC) on the genome of the mouse hematopoietic stem cells (HSCs) and thereby increases the HSC self-renewal capability accompanied by defective differentiation and develop human myelodysplastic syndrome (MDS)-like disease and hematological malignancies. Interestingly, miR-22 appears to be overexpressed in human MDS and leukemia and its aberrant expression correlates with poor survival of patients. Ultimately, our findings will offer the therapeutic potentials of a targeting of miR-22 as a treatment modality for cancer hallmarks.

 ▶Inquiry: Prof. Tae-Young Roh (279-2350)