Abstract 2232: Down-regulation of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A mediated by miR-1246 and miR-1290 in multiple myeloma cancer stem-like cells

Multiple Myeloma (MM) is a clonal plasma cell derived malignancy characterized with high relapse rate and fatality despite recent therapeutic advances. The existence of the rare population of CD138neg cancer stem-like cells had been identified and demonstrated to bear higher clonogenicity and self-renewal capacity when compared to the CD138pos major population. Besides, CD138neg MM cells are more resistant to common therapeutic agents treating MM including dexamethasone, lenalidomide and bortezomib. Therefore, targeting MM cancer-stem like cells could be critical to achieve a cure in MM. Previously, our lab had identified 2 microRNAs, miR-1246 and miR-1290 that are overexpressed in CD138neg MM cells in both cell lines and patient samples. Their target genes are being studied in the present study. CD138pos and CD138neg MM cells were isolated using MACS-immunomagnetic system and the purity of both CD138neg and CD138pos fraction were accessed by flow cytometry using PE anti-human CD138 antibody. The purity of each fraction was over 95% in 4 cell lines (U266, RPMI8226, OPM2 and KMS-12-PE) used. mRNA level of 7 putative targets (DYRK1A, KDM5A, NKRF, STK17A, PHLDA1, FOXA1, SCAI) chosen from TargetScan 6.2, miRanda or previous studies, which are related to tumor development in other cancers, of miR-1246 or miR-1290 were examined using RT-qPCR. Among the 7 putative targets, DYRK1A, KDM5A and NKRF were down-regulated in all four cell lines used. 3′UTR of the 3 down-regulated targets were cloned into pmirGLO Dual-Luciferase miRNA Target Expression Vector, which were co-transfected with miRNA-mimic into 293FT cells. Down-regulation of luciferase signal was observed in DYRK1A (p Citation Format: Terry Hei Yan Wong, Coty HY Cheung, Natalie Pui Ha Chan, Rosalina KL Ip, Chi-Keung Cheng, Kitty Ka Yan Ng, Margaret H.L. Ng. Down-regulation of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A mediated by miR-1246 and miR-1290 in multiple myeloma cancer stem-like cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2232. doi:10.1158/1538-7445.AM2015-2232