RESULTS

Identification of microRNA associated with chemoresistance and stemness in pancreatic cancer (Br. J Cancer, 111, 1572, 2014)

Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumor recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterize the clinical significance. In collaboration with Osaka University and Tokyo University, Hasegawa et al. established chemo-resistant pancreatic cancer cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumorigenicity. The expression was studied in pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR expression via a target. In vivo, we found that the miR could increase tumor-initiating potential and induced drug resistance. A high expression level of miR was correlated with a worse prognosis and the target expression was significantly lower in those patients.The data indicated that the miR expression was associated with chemoresistance and CSC-like properties via a target pathway, and could predict worse prognosis in pancreatic cancer patients. Detailed information will be available in publication.