From: Role of epigenetics-microRNA axis in drug resistance of multiple myeloma
Sample source | Epigenetic modifiers | miRNAs targeted | Targets/pathways modulated by miRNA | Functional outcomes | Refs. |
---|---|---|---|---|---|
MM cell lines (NCI-H929, U266, KMS11, OPM2, RPMI8226, MM1.S) and MM primary samples | DNA methylation (DNMTs) | miR-137 | AURKA/p-ATM, p-Chk2 | Induction of drug resistance to bortezomib and epirubicin, chromosomal instability | [52] |
MM cell lines (MM1S, H929, OPM-2, JJN3, and RPMI 2886) | DNA methylation (DNMTs) | miR-214 | PSMD10 & ASF1B/p53-MDM2 | A significant enrichment for DNA replication and induction of cell proliferation, and as a consequence also in cell survival | [87] |
MM cell lines (NCI-H929 and U-266, KMS-12-PE, LP-1, OPM-2) and MM primary samples | DNA methylation (DNMTs) | miR-124-1 | CDK6 | Induction of cell proliferation | [50] |
MM cell lines (KMS11, SKMM1, and NCI-H929) and PCL and MM primary samples | HDACs | miR-29b | Mcl1/SP1 and HDAC4 | Induction of cell growth by upregulation of pro-survival proteins (MCL-1 and SP1) | [63] |
MM cell lines (MM.1S, LP1, H929, and JJN3) | HDACs | miR-9-5p | IGF2BP3/CD44 | CD44 overexpression, a glycoprotein that has been associated with lenalidomide and dexamethasone resistance in myeloma | [90] |
MM cell lines (INA-6, LP-1, L363, KMS-11) and MM primary samples | EZH2 | miR-125a-3p & miR-320c | RF-4, XBP-1, BLIMP-1, c-MYC | Upregulation of oncogenes and inhibit apoptosis | [29] |
MM cell lines RPMI8226 and U266 | EZH2 | miR-101 | E-cadherin, MMP9, c-Myc, cyclin D3, CDK4, and CDK6 | Induction of cell proliferation and inhibit apoptosis | [91] |