From: Role of epigenetics-microRNA axis in drug resistance of multiple myeloma
miRNAs | Dysregulation | Outcome | Refs. |
---|---|---|---|
miR-21 | Upregulation | Inhibition of apoptosis and increase drug resistance | [74] |
miR-125b | Upregulation | Reduction of cell death in dexamethasone induced MM (drug resistance) | [75] |
miR-15a miR-16 | Downregulation | Regulation of MM cell proliferation in vitro and in vivo Downregulated in patients with relapsed/refractory disease (drug resistance) | |
miR-221/222 | Upregulation | Inhibition of apoptosis and modulation of drug influx-efflux and ABC transporters (drug resistance) | [36] |
miR-27a | Downregulation | Downregulated in MM patients with bortezomib-refractory status (drug resistance) | [46] |
miR-149 | Downregulation | Downregulated in glucocorticoid resistant MM cells by disturbing epigenetic landscape, leading to overexpression of MMP-9 gene which is involved in bone remodeling and tumor invasion in MM | [78] |
miR-631 | Downregulation | Modulates UbcH10/MDR1 pathway which is associated with the development of BTZ resistance in myeloma cells | [79] |
miR-202 | Downregulation | Involved on drug resistance of MM cells by targeting JNK/SAPK signaling pathway | [80] |
miR-30c | Downregulation | Downregulated as a result of interaction between MM cells and bone marrow stromal cells, which in turn activation of oncogenic Wnt/β-catenin/BCL9 pathway and promote MM cell proliferation, drug resistance and formation of MM cancer stem cells. | [81] |
miR-137/197 | Downregulation | Modulates MCL-1 which is dysregulated in multiple myeloma cells and overexpression of MCL-1 is associated with relapse and poor survival | [51] |
miR-17-92 cluster miR-106~363 cluster | Upregulation | High level is associated with shorter overall survival | [82] |
miR-148a & miR-20a | Upregulation | Shorter relapse-free survival | [83] |
let-7e, miR-125a-5p, and miR-99b cluster | Upregulation | Overexpression in t(4;14) patients | [84] |
miR-140-3p | Downregulation | Altered expression due to the occurrence of several allelic imbalances or loss of heterozygosity in 16q2 region | [84] |
miR-32 and miR-17~92 cluster | Upregulation | Upregulated in MM patients and cell lines but not in MGUS or healthy PCs | [85] |
miR-19a and 19b | Upregulation | Inhibition of IL-6 growth signaling | [85] |
miR106b~25 cluster, miR-181a/b, miR-32 | Upregulation | Targeting of the genes which involved in p53 regulation | [85] |
miR-1/miR-133a cluster | Upregulation | Overexpressed in MM patients with t(14;16) | [86] |
miR-135b and miR-146a | Downregulation | Downregulated in MM with t(4;14) and targeted the genes which are involved in IL-1 signaling pathway | [86] |
miR-214 | Downregulation | Positive regulation of P53 and inhibition of DNA replication | [87] |
miR-29b | Downregulation | Reduction of apoptosis by upregulation of MCL1 | [88] |
miR-192, miR-194, miR-215 | Downregulation | p53-inducible microRNAs which modulate MDM2 expression regulate IGF pathway and enhance migration of plasma cells into bone marrow | [89] |