Table 3. Summary of cancer-associated editing events regulating miRNA biogenesis and activity.
Editing events have been grouped into three categories based on whether they affect miRNA target specificity, binding or biogenesis and processing. Additional details including the type of cancer the editing event is found in, ADAR enzyme responsible, targets identified and associated mechanism (where known) has been provided along with respective references.
| Editing alters miRNA target specificity | ||||||
|---|---|---|---|---|---|---|
| miRNA | ADAR | Target(s) | Function | Cancer | Reference | |
| Unedited | Edited | |||||
| miR-200b | ADAR1 & ADAR2 | ZEB1 ZEB2 |
LIFR | –Wild type miR-200b inhibits cell migration and invasion –Edited miR-200b acts upon Leukemia Inhibitory Factor Receptor (LIFR), a gene known to suppress Epithelial-to-Mesenchymal transition (EMT) and aids tumor metastasis |
BRCA, HNSC, COAD, KICH, KIRC, LUAD, STAD, THCA, UCEC | (Ramirez-Moya et al., 2020; Wang et al., 2017) |
| miR-379–5p | ADAR2 | PTK2 | CD97 | –Unlike wild type, edited miR-379–5p inhibits cellular proliferation and promotes apoptosis | CRC, HNSC, LUAD, LUSC, SC, THCA, UC | (Xu et al., 2019) |
| miR-455–5p | ADAR1 | CPEB1 | RhoC MDM4 Integrin ⍺2 |
–Through regulation of tumor suppressor CPEB1, wild type miR-455–5p promotes tumor growth and metastasis –ADAR1-mediated editing of miR-455–5p inhibits expression of mature miRNA and suppresses melanoma progression |
Melanoma | (Shoshan et al., 2015) |
| miR-378a-3p | ADAR1 | – | PARVA | –PARVA promotes tumor growth and invasion through increased expression of MMP-2 and c-Jun | Melanoma | (Velazquez-Torres et al., 2018) |
| miR-376a* | ADAR2 | RAP2A | AMFR | –Wild type miR-376a* promotes tumor cell proliferation, migration and invasion through suppression of RAP2A –Edited miR-376a* inhibits tumor progression through regulation of AMFR |
GBM | (Choudhury et al., 2012) |
| miR-589–3p | Primarily ADAR2 | PCDH9 | ADAM12 | –In contrast to wild type miRNA, edited miR-589–3p suppresses tumor cell proliferation and motility –Edited miR-589–3p also suppresses MMP9 activity |
GBM | (Cesarini et al., 2018) |
| Editing alters miRNA binding | ||||||
| miRNA | ADAR | Target(s) | Function | Cancer | Reference | |
|
miR-25–3p miR-125a-3p |
ADAR1 | DHFR | –Editing of the DHFR 3’ UTR disrupts miR-25–3p and miR-125a-3p binding sites DHFR promotes cell viability |
BRCA | (Nakano et al., 2017) | |
|
miR-30b-3p miR-573 |
ADAR1 | ARHGAP26 | –Editing of the ARHGAP26 3’ UTR disrupts miR-30b-3p and miR-573 binding sites –ARHGAP26 inactivates oncogenic proteins RhoA and Cdc42 |
BRCA, GBM | (Wang et al., 2013) | |
| Editing alters miRNA biogenesis and processing | ||||||
| miRNA | ADAR | Target(s) | Function | Cancer | Reference | |
| miR-21 | ADAR2 | PDCD4 | –Mature miR-21 promotes tumor migration –Editing inhibits mature miR-21 expression |
GBM | (Tomaselli et al., 2015) | |
| miR-221/222 | ADAR2 | p27Kip1 | –Mature miR-221/-222 promotes tumor cell proliferation –Editing inhibits mature mi221/222 expression |
GBM | (Tomaselli et al., 2015) | |
| miR-214 | ADAR2 | Rab15 | –Editing of the transcript antisense to pri-miR-214 decreases expression of mature miR-214 –miR-214 inhibition is associated with an increase in metastatic phenotype through regulation of Twist and E-Cadherin expression |
HCC | (Li et al., 2012; Liu et al., 2013) | |
| miR-222 | ADAR1 | ICAM1 | –Editing decreases miR-222 expression and inhibits suppression of ICAM1 expression | Melanoma | (Galore-Haskel et al., 2015) | |
# represents bioinformatically predicted targets.
Abbreviations Used: (see Table 2 legend as well) Colon Adenocarcinoma (COAD), Kidney Chromophobe (KICH), Stomach Cancer (SC), Uterus Cancer (UC), Uterine Corpus Endometrial Carcinoma (UCEC)