Abstract: Objective To explore the molecular mechanisms of c-Myc / miR-27b-3p / Bcl-2 axison promoting multiple myeloma ( MM) cell survival. Methods The relative expression levels ofMM-related genes and microRNAs (miRNAs) were measured in human MM cell lines RPMI8226 and U266 cells by using qPCR analysis. TargetScan and dual-luciferase gene reporter assay were used to predict and verify the targeting relationship between miR-27b-3p and Bcl-2, respectively. The primary MM cells were isolated from 14 patients with MM recruited from the Fifth Affiliated Hospital of Xinjiang Medical University. The mRNA expression levels of c-Myc, Bcl-2, and the expression level of miR-27b-3p in primary MM cells were detected by qPCR. Pearson correlation analysis was used to analyze the relationship among their expression levels. Adenovirus vectors with c-Myc or Bcl-2 overexpression ( Bcl-2 OE, c-Myc OE), or miR-27b-3p inhibitor ( miR-27b-3p inhibitor) were constructed and transfected into the BMSCs. The expression levels of p-STAT3, STAT3,p-JAK2, and JAK2 in BMSCs were detected by Western blotting. Results Compared with those in the BMSCs, the mRNA expression levels of c-Myc and Bcl-2 were upregulated in the RPMI8226cells and the U266 cells (P < 0. 01), and miR-27b-3p was downregulated in the RPMI8226 cells and the U266 cells (P< 0. 01). Dual-luciferase gene reporter assay results showed that miR-27b-3p was directly targeted to the Bcl-2 3′-UTR. qPCR and Pearson correlation analysis showed that therelative expression levels of c-Myc mRNA and miR-27b-3p, miR-27b-3p and Bcl-2 mRNA werelinearly and negatively correlated (P< 0. 01), while the relative expression levels of c-Myc mRNA and Bcl-2 mRNA were linearly and positively correlated ( P < 0. 01). Compared with those in theBMSCs group, the expression levels of p-STAT3, STAT3, p-JAK2, and JAK2 in the BMSCs + cMyc OE group, the BMSCs + miR-27b-3p inhibitor group, and the BMSCs + Bcl-2 OE group wereall increased (P< 0. 05). Conclusion c-Myc upregulation and miR-27b-3p inhibition activated theBcl-2 to promote cell survival in MM.

Key words: multiple myeloma, c-Myc, miR-27b-3p, Bcl-2, JAK2 / STAT3, cell survival