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- W3174965330 abstract "Abstract Objective: Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that could regulate gene expression in eukaryotes. Glucocorticoid resistance is the primary factor of refractory relapse in patients with multiple myeloma (MM). This study was designed to reveal the role of circPVT1 in mediating glucocorticoid resistance in MM through regulating its target genes to inhibit apoptosis of MM cell and promote tumor stem cell survival. Methods and results: We determined with RT-PCR assay that circRNA PVT1 is differentially expressed between glucocorticoid resistant and sensitive MM cells (Figure A), and is closely correlated with prognosis (Figure G and H). We further investigated the role of circPVT1 in MM cell apoptosis and proliferation as well as its downstream signaling pathway mechanism. Silencing circPVT1 enhances sensitivity to glucocorticoid treatment (Figure D), promotes apoptosis and inhibits cell proliferation in resistant MM cell lines and myeloma cells in NOD-SCID mice, resulting up-regulation of the apoptosis pathway as measured by increased Caspase3, PARP and decreased Bcl-2 (Figure E). Measured by CCK-8 cell viability assay, ectopic expression of circPVT1 contributed to inducing proliferation and suppressing apoptosis in sensitive MM cell lines. Using Hoechst Staining, we found that MM stem cell population increases upon ectopic expression and decreases while silencing circPVT1, which revealed circPVT1 could facilitate the proliferation of stem cells to enhance glucocorticoid resistance (Figures F and I). Conclusion: As a downstream of circPVT1, it promotes c-myc nuclear translocation, which intermediated by miRNAs to enhance its targets thus promotes the proliferation of stem cells and inhibits apoptosis. We concluded that circPVT1 may mediate MM glucocorticoid resistance and its downstream signaling pathway may represent a novel target for MM treatment. Figure (A)RT-PCR showing the differential expression of circPVT1 and linear RNA PVT1 between MM.1R and MM.1S cell lines.** P Download : Download high-res image (117KB) Download : Download full-size image Figure . Disclosures No relevant conflicts of interest to declare." @default.
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- W3174965330 date "2017-12-08" @default.
- W3174965330 modified "2023-09-29" @default.
- W3174965330 title "CircPVT1 Inhibit Apoptosis and Enhance Drug Resistance in Multiple Myeloma" @default.
- W3174965330 doi "https://doi.org/10.1182/blood.v130.suppl_1.3085.3085" @default.
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