MicroRNA(or miRNA) regulates various biological process including development, differentiation, proliferation, maintenance and apoptosis. Recently, existence of cancer stem cells was reported in some solid malignancies, including breast, brain, prostate, liver and pancreas cancers. Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that is virtually therapy-resistant. Thus better understanding on cancer stem cell biology will not only help us to develop diagnostic marker for early diagnosis but also to treat against chemoresistant pancreatic cancer. Lately, evidences of miRNA involvement in cancer stem cells have been reported. Several miRNAs including let-7, mir-200, and mir-181 shows regulatory functions in cancer stem cells of different organs, however, miRNAs in other cancers including pancreas has not yet been reported. In this present study, we analyzed pancreatic cancer stem cell specific miRNAs and further investigated their functional role in cancer stem cells.

To analyze the differentially expressed miRNAs, we used sphere cultivation methods to enrich stem cell population and analyzed overall miRNA expression with miRNA microarray. Then correlation of miRNA expression and mRNA expression was analyzed by using linear model Yijkg=µ+Ai+Dj+Vk+Gg+AGig+VGkg+εijkg where A, D, V, and G represent the additive effect of the ith array, jth dye, kth biological group, and gth gene, respectively; AG represents the combinatorial effect of the ith array with the gth gene; εijkg describes the random error associated with each measurement; and VG for the combinatorial effect of the kth biological group with the gth gene. All additive effects were estimated via least squares and an F-test was performed on the modeled data to select differentially expressed genes. The candidate miRNA expression was confirmed by qRT-PCR.

As a result, number of miRNAs showed differential expression in sphere and are considered to have functional role in cancer stem cells by directly or indirectly targeting mRNAs. Further, correlation analysis suggested possible linkage between miRNA clusters with stem cell associated mRNAs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3023.