Role of MicroRNA in Aggressive Prostate Cancer
Annual rept. 15 June 2013 - 14 June 2014
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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The majority of mortality of prostate cancer PCa is due to the recurrent metastasized castration resistance PCa. The acquisition of epithelial to-mesenchymal transition EMT in PCa signifies the initial process of cancer metastasis. Our previous findings unveiled that DAB2IP is down-regulated in high-grade PCa specimens and this novel tumor suppressor can block EMT leading to lymph node metastasis. It has recently been associated with the onset of cancer stem cell CSC that is considered as cancer initiating cell with a survival advantage during the course of cancer therapy. However, the mechanism of action is not fully characterized. Using microRNA microarray screening, we found microRNA-363 miR363 is significantly down regulated in several DAB2IP knockdown KD prostate cells. In particular, miR363 is predominately expressed in normal prostate and belongs to the miR106a-363 cluster that is closely resembled to the oncogenic miR17-92 cluster in their seed sequence. It appears that DAB2IP significantly regulates the expression of a unique miR-363 the profile of miR-363 expression appears to be highly specific in normal prostate. The objective of this project is to delineate the functional links of miR-363 with the appearance of CSC and its clinical correlation in aggressive PCa.
- Medicine and Medical Research