Table 2. Summary of recoding editing events previously shown to regulate tumor progression in different tissues.
Recoding events are classified into tumor promoting or inhibiting. Additional provided details include cancer type, ADAR enzyme responsible for editing and oncogenic mechanism (where known).
| Editing promotes cancer growth and progression | ||||||
|---|---|---|---|---|---|---|
| Gene | Protein | Editing Site | ADAR | Mechanism | Cancer | Reference |
| AZIN1 | Antizyme Inhibitor 1 | S367G | ADAR1 | –Edited AZIN1 binds to Antizyme 1 with a stronger affinity and inhibits degradation of oncoproteins –Editing of AZIN1 is probably also associated with cytoplasmic-to-nuclear translocation |
HCC, CRC, ESCC, NSCLC | (Chen et al. 2013; Qin et al. 2014; Hu et al. 2017; Shigeyasu et al. 2018) |
| BLCAP | Bladder Cancer Associated Protein | Y2C | ADAR1 | –Edited BLCAP increases phosphorylation and activation of Akt/MDM2/mTOR and inhibits p53 phosphorylation | HCC | (Galeano et al. 2010; Hu et al. 2015) |
| Y2C; Q5R; K15R | ADAR1 & ADAR2 | –Edited BLCAP prevents inhibition of STAT phosphorylation, promoting IL6-mediated JAK-STAT signaling | CC | (Galeano et al. 2010; Chen W et al. 2017) | ||
| COG3 | Component of Oligomeric Golgi Complex 3 | I635V | ADAR2 | N.D. | GBM, LGG, BRCA, HNSC, KIRC, KIRP, LUAD, LUSC, STAD, THCA, SARC, SKCM | (Han L et al. 2015; Peng et al. 2018) |
| COPA* | COPI Coat Complex Subunit Alpha | I164V | ADAR2 | –In HCC, unedited COPA promotes tumor cell proliferation and clonogenicity. –Upon editing, COPA serves as tumor suppressor and downregulates CAV1-mediated PI3K/AKT/mTOR pathway |
SARC, SKCM, LGG, BRCA, GBM, HNSC, KIRC, LUAD, LUSC, STAD, ESCA, HCC | (Chan et al. 2014; Han L et al. 2015; Peng et al. 2018; Song et al. 2020) |
| FLNB | Filamin B | M2269V | ADAR1 & ADAR2 | N.D. | HCC, ESCC | (Chan et al. 2014; Qin et al. 2014) |
| Q2327R | ADAR2 | PCPG, KIRC, LGG, SKCM, SARC | (Peng et al. 2018) | |||
| GLI1 | Glioma-Associated Oncogene 1 | R701G | ADAR1 | –Editing disrupts SUFU (Suppressor of Fused Homolog)-mediated inhibition of GLI1 activity/hedgehog signaling | MM | (Lazzari et al. 2017) |
| NEIL1 | Nei Like DNA Glycosylase 1 | K242R | ADAR1 | –Edited NEIL1 has impaired oxidative damage and single-strand break (SSB) DNA repair abilities, which predisposes cells to double-strand breaks (DSBs) and increased sensitivity towards DSB inducing agents | MM | (Teoh et al. 2018) |
| RhoQ | Ras homologue family member Q | N136S | N.D. | –Editing increases RhoQ activity –Editing promotes actin cytoskeletal remodeling and tumor invasion |
CRC | (Han SW et al. 2014) |
| SLC22A3 | Solute Carrier Family 22 Member 3 | N72D | ADAR2 | –SLC22A3 inhibits cytoskeletal remodeling by sequestering ACTN4 to the cell membrane Edited SLC22A3 relieves ACTN4 suppression and promotes tumor metastasis |
ESCC | (Fu et al. 2017) |
| Editing promotes cancer growth and progression | ||||||
| Gene | Protein | Editing Site | ADAR | Function | Cancer | Reference |
| CCN1 | Cyclin I | R75G | ADAR1 | –Peptide derived from edited CCN1 is presented by MHC molecules on tumor cell surfaces and elicits antitumorigenic immune responses | Melanoma | (Zhang et al. 2018) |
| GABRA3 | Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha 3 | I342M | ADAR1 | –Edited GABRA3 promotes tumor suppression by acting in a dominant negative manner to reduce cell surface expression of unedited GABRA3 and inhibition of Akt phosphorylation | BC | (Gumireddy et al. 2016) |
| GLI1 | Glioma-Associated Oncogene 1 | R701G | ADAR1 & ADAR2 | –Editing prevents SUFU-mediated inhibition of GLI1 and reduces GLI1 activation by Dyrk1a kinase | MB, BCC | (Shimokawa et al. 2013) |
| GRIA2 | Glutamate Ionotropic Receptor AMPA Type Subunit 2 | Q607R | ADAR2 | –Edited GRIA2 inhibits Ca2+ influx mediated Akt Phosphorylation | Gliomas | (Maas et al. 2001; Cenci et al. 2008) |
| IGFBP7 | Insulin Like Growth Factor Binding Protein 7 | K95R | ADAR2 | –Editing protects IGFBP7 from matriptase-mediated proteolysis thereby promoting apoptosis | ESCC | (Chen YB et al. 2017) |
| PODXL** | Podocalyxin Like | H241R | ADAR2 | N.D. | GC | (Chan et al. 2016) |
COPA under-edited in Hepatocellular and Gastric Carcinoma (Chan et al., 2014; Chan et al., 2016)
ADAR1 edits PODXL resulting in a synonymous T238T mutation. However, both ADAR1 and ADAR2 cannot edit PODXL simultaneously. As a result, this synonymous editing event is capable of inhibiting ADAR2-mediated non-synonymous PODXL editing.
Abbreviations Used: Not determined (N.D.), Breast Cancer (BC), Basal Cell Carcinoma (BCC), Breast Invasive Carcinoma (BRCA), Cervical Cancer (CC), Colorectal Cancer (CRC), Esophageal Carcinoma (ESCA), Esophageal Squamous Cell Carcinoma (ESCC), Gastric Cancer (GC), Glioblastoma (GBM), Hepatocellular Cancer (HCC), Head And Neck Squamous Cell Carcinoma (HNSC), Kidney Renal Clear Cell Carcinoma (KIRC), Kidney Renal Papillary Cell Carcinoma (KIRP), Lower Grade Glioma (LGG), Lung Adenocarcinoma (LUAD), Lung Squamous Cell Carcinoma (LUSC), Medulloblastoma (MB), Multiple Myeloma (MM), Non-Small Cell Lung Carcinoma (NSCLC), Pheochromocytoma and Paraganglioma (PCPG), Sarcoma (SARC), Skin Cutaneous Melanoma (SKCM), Stomach Adenocarcinoma (STAD), Thyroid Carcinoma (THCA)