Inhibition of STAT3 Signaling in Multiple Myeloma

Example 3

Human multiple myeloma cancer cells are known to undergo increased cell division through IL-6-triggered STAT3 signaling. Numerous studies have shown that let7a-3p miRNA (SEQ ID NO:1), let7a-5p miRNA (SEQ ID NO:2), miR17-3p miRNA (SEQ ID NO:3), miR17-5p miRNA (SEQ ID NO:4), or miR218-5p miRNA (SEQ ID NO:5) inhibits the activity of transcription factor Signal Transducer and Activator of Transcription 3 (STAT3). Human multiple myeloma cells MM.1S were incubated for 48 hrs daily with 10 μg/ml modified miRNA as indicated and expression of the STAT3 target genes was analyzed by RT-PCR. As shown in FIGS. 2C, 4C, 6C, 8C and 10C, incubation with PS-modified let7a-3p miRNA (SEQ ID NO:1), let7a-5p miRNA (SEQ ID NO:2), miR17-3p miRNA (SEQ ID NO:3), miR17-5p miRNA (SEQ ID NO:4), or miR218-5p miRNA (SEQ ID NO:5) inhibited expression of STAT3 target genes, for example, oncogenic Bcl-xL and/or IL-6 genes.