Table 1.
A summary of lncRNAs that regulate gene expression in AML and their roles in leukemia cells.
| LncRNA | Putative role | Function in AML cells | Mechanism of action | References |
|---|---|---|---|---|
| HOTAIRM1 | Tumor suppressor | Regulates myeloid maturation, cell cycle, and autophagy | Activates proximal HOXA and CD11b/CD18/CD11c expression and represses CD49d; sponges miR-20a/miR-106b/miR-125b | (46–49) |
| HOXA-AS2 | Oncogenic | Mediates resistance to apoptosis and Adriamycin | Sponges miR-520c-3p, thereby increasing S100A4 | (50, 51) |
| HOTAIR | Oncogenic | Promotes leukemic phenotypes by modulating c-KIT and p15 | Sponges miR-193a away from c-KIT and epigenetically silences p15, perhaps via PRC2 or LSD1? | (52, 53) |
| CCAT1 | Oncogenic | Inhibits myeloid maturation and promotes proliferation | Sponges miR-155 away from c-MYC | (54) |
| UCA1 | Oncogenic | Promotes chemoresistance, glycolysis, and proliferation; activated by CEBPα-p30 | Sponges miR-125a away from HK2, and miR-126 from RAC1; translationally represses p27! | (55–57) |
| PU.1-AS | Oncogenic* | Negatively regulates PU.1 expression | Interferes with PU.1 translation by binding eIF4A | (58) |
| IRAIN | Tumor suppressor° | Regulates expression of IGF1R in cis | Mediates enhancer looping to IGF1R promoter | (59) |
| PVT1 | Oncogenic | Regulates expression of MYC in cis; promotes proliferation and survival | Alternate TSS are enhancers that loop to MYC!; promoter acts as a DNA boundary element? | (60–62) |
| RUNXOR | Oncogenic° | Upregulated in AML blasts and after Ara-C treatment!; likely regulates RUNX1 | Interacts with chromatin to form intra/interchromosomal loops, and with RUNX1 and EZH2 | (63) |
| GAS6-AS2 | Oncogenic | Mediates resistance to cytarabine (Ara-C) | Positively regulates GAS1 and AXL expression in the latter case via promoter methylation by DNMT! | (64) |
| TUG1 | Oncogenic | Confers Adriamycin resistance | Epigenetically silences miR-34a via EZH2-dependent deposition of H3K27me3 at the promoter | (65) |
| MIR100HG/MONC | Oncogenic | Required for maintenance and self-renewal of AMKL | Enhances erythroid progenitors | (66) |
| LINC-223 | Tumor suppressor | Promotes monocytic differentiation | Acts as a decoy against oncogenic miR-125 family members | (67) |
| ANRIL | Oncogenic | Maintains AML cell survival/proliferation and regulates glucose metabolism | Activates ADIPOR1/AMPK/SIRT1 expression | (68) |
| NEAT1 | Tumor suppressor | Decreases proliferation and increases apoptosis | May act as a ceRNA on the miR-23a-3p/SMC1A axis | (69) |
| H19 | Oncogenic | Behaves like an oncogenic lncRNA; may be involved in telomerase activity | May act as a ceRNA on miR-19/ID2; mediates hTERT2/hTR interaction | (70–72) |
| CASC15 | Oncogenic* | Promotes myeloid over B-cell development≠ | May positively regulate SOX4 transcription via YY1? | (73) |
| CCDC26 | Tumor suppressor* | May regulate cellular response to starvation! | May negatively regulate c-KIT! | (74) |
| MEG3 | Tumor suppressor | Acts as a tumor suppressor, is regulated by WT1/TET2 | Activates p53, downregulates DNMT3A through MDM2/RB1 | (75) |
| WT1-AS | Tumor suppressor* | Mediates WT1 induction under hypoxic conditions | Regulates WT1 expression in cis | (76) |
The order corresponds to their sequence of appearance in the manuscript. The lncRNAs are grouped according to their mechanisms of action, with different groups separated by double lines in the table.
?
Mechanism described in other tumor contexts; remains to be confirmed in AML.
!
Mechanism described in K562 cells (chronic myeloid leukemia, CML); implicated in AML.
*
Speculation based on the regulation of coding genes; cellular phenotype not yet characterized.
°
Speculation based on expression levels in patient samples; cellular phenotype not yet characterized.
≠
Experiment conducted in the murine system; remains to be validated in human cells.