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Table 2 Summary of key epigenetic modifiers found in MM and their miRNA targets

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]