Table 1.
Brief summary of the DNA methylation status and function of miRNA in MM.
| miRNA | Methylation Status in NPC, MM and HMCLs |
Function in MM | Ref. |
|---|---|---|---|
| 9-3 and 9-1 | Unmethylated in MM, methylated in HMCLs | CD44 overexpression, (glycoprotein that has been associated with lenalidomide and dexamethasone resistance in myeloma) | [63,64] |
| 10b-5p | Methylated in MM Upregulated after 5-aza-CdR in HMCLs |
Not tested | [48] |
| 28 | Unmethylated in healthy controls and at MM relapse, methylated in some HMCLs | Inverse correlation between CCND1 expression and LPP/miR-28 methylation | [65] |
| 34a | Methylated in primary MM, no difference between diagnosis and relapse, highly methylated in HMCLs | Inhibition of MM growth and reduction of bone lesions by targeting TGIF2 | [47,66] |
| 34b/c | Methylated in MM, increased methylation in relapsed MM, highly methylated in HMCLs | Inhibition of cellular proliferation and induction of apoptosis in MM cells | [50] |
| 124-1 | Methylated in primary MM, highly methylated in HMCLs | Repression of CDK6 | [67] |
| 129 | Methylation increases from MGUS to MM at diagnosis and at relapse/progression | Downregulation of SOX4 | [51] |
| 152 | Highly methylated in MM and in HMCLs Upregulated after 5-aza-CdR in HMCLs Targets DNMT1 |
Decrease of DNMT1 and E2F2 Induction of apoptosis in MM cells | [48] |
| 155 | Highly methylated in HMCLs Expression induced by LPS only when unmethylated in HMCLs |
High expression of miR-155 was associated with improved overall survival (OS) in MM. | [68] |
| 192, 194 and 215 | Methylated in MM cell lines | High expression of miR-194 was associated with improved OS in MM. Overexpression associated with inhibition of cellular proliferation and migration |
[28] |
| 198, 135a*, 200c, 125a-3p, 188-5p, 483-5p, 663, 630 | Methylated in MM Upregulated after 5-aza-CdR in HMCLs |
Not tested | [69] |
| 203 | Methylated in HMCLs | Downregulation of CREB1 protein and inhibition of proliferation of myeloma cells | [49] |
| 342-3p | Methylated in MGUS and increased methylation in relapsed MM Upregulated after 5-aza-CdR in HMCLs |
Not tested | [52] |
| 375 | Methylated in MM and HMCLs | Downregulation of PDPK1 and IGF1R | [53] |
Abbreviations: normal plasma cells (NPC), multiple myeloma (MM), Monoclonal gammopathy of undetermined significance (MGUS) and human myeloma cell lines (HMCLs).