Furthermore, to accurately predict the optimal target genes of MM, the logFC, targetScanCS and targetScanPCT values of known genes in four miRNAs (i.e. has-miR-21, has-miR-20a, has-miR-148a and has-miR-99b) were used to compute the targetScore values.
In this study, we investigated the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR-21 and miR-146a in these effects.
In previous studies we identified microRNA-21 as a STAT3 target gene with strong anti-apoptotic potential, suggesting that noncoding RNAs have an impact on the pathogenesis of human multiple myeloma.
The grayscale value of protein bands demonstrated that SPRY2 protein expression significantly decreased in miR‑21 mimic‑transfected U‑266 cells compared with that in the inhibitor‑transfected, siRNA‑transfected and untreated cells (P<0.01). miR‑21 may represent a negative regulator involved in the downregulation of SPRY2 in MM. miR‑21 is closely associated with the pathogenesis, progression and prognosis of MM and may thus be used as an indicator of poor MM prognosis.
Real-time quantitative PCR and western blot analysis showed that in the MM cell lines with high endogenous miR-21 expression (RPMI8226 and KM3), SPRY2 expression was significantly lower.
Taken together, our data provide proof-of-concept that miR-21 overexpression within MM-microenviroment plays a crucial role in bone resorption/apposition balance, supporting the design of innovative miR-21 inhibition-based strategies for MM-related BD.
In this review, we aim at summarizing the current knowledge of miR-21 functions in MM, with an emphasis on its laboratory research and clinical research in MM.
Down-regulation of interleukin 6 (IL6) by berberine might lead to inhibition of miR-21 transcription through STAT3 down-regulation in multiple myeloma.
Conversely, transfection of miR-21 mimics significantly increased proliferation of multiple myeloma cells, showing its tumor-promoting potential in multiple myeloma.
This elucidation of the role of PIAS3 in the miR-21-STAT3 positive regulatory loop not only may shed light on the molecular basis of the biological effects of miR-21 observed in MM cells but also has direct implications for the development of novel anti-MM therapeutic strategies.