Table 1.

RNA editing in transcripts involved in cancer biogenesis or progression, reported in patient samples

Gene name	Protein function [edited protein function]	RNA editing effect on protein level	Cancer type	Comments	Reference article	System in which the effect of editing event was studied
Cancer progression step: initiation and promotion
NEIL1	The NEIL1 enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. [The edited isoform of NEIL1 shows reduced ability to repair oxidative damage in DNA. Single-stranded DNA breaks predispose cells with more unedited NEIL1 isoform to double-stranded DNA breaks and activate double-stranded break repair proteins, ultimately promoting cell growth and survival]	K242R	Non-small cell lung cancer	increased ADAR1-mediated A-to-I RNA editing	[95]	Cell lines, mouse
			Multiple myeloma	ADAR1-mediated A-to-I RNA editing	[96]	Cell lines
Cancer progression step: cancer survival and proliferation
AZIN1	AZIN1 plays a role in cell growth and proliferation by maintaining polyamine homoeostasis within the cell. [The edited isoform of AZIN1 has increased affinity to antizyme therefore causing increased cell proliferation. Antizyme is a protease that degrades other proteins, including an enzyme involved in synthesizing spermidine]	S367G	Hepatocellular carcinoma	increased level of A-to-I RNA editing by at least 10% was observed	[107]	Cell lines, mouse (xenografts)
			Oesophageal squamous cell carcinoma	ADAR1-mediated A-to-I RNA editing	[97]	Cell lines, mouse (xenografts)
			Non-small cell lung cancer	aberrantly edited	[118]	Cell lines, mouse
			Breast cancer	ADAR1-mediated A-to-I RNA editing	[116]	Cell lines
			Colorectal cancer	ADAR1-mediated A-to-I RNA editing	[117]	Cell lines, mouse (xenografts)
GLI1	GLI1 is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. [In multiple myeloma, the edited isoform of GLI1 activates the Hedgehog signalling pathway, which when activated in adults, may promote malignant cell proliferation. In contrast, edited GLI1 in basal cell carcinoma and medulloblastoma has the opposite effect than in multiple myeloma – it manifests reduced oncogenic potential as it is less accessible for its activator DYRK1A]	R701G	Multiple myeloma	ADAR1-mediated A-to-I RNA editing	[119,120]	Cell lines
BLCAP	BLCAP is a tumour suppressor gene required for growth inhibition, S phase arrest, and apoptosis. [Increased editing of BLCAP coding region promotes cell proliferation via enhanced phosphorylation of AKT, mTOR, and MDM2 (negative regulator of P53) and inhibition of P53 phosphorylation. Multiple RNA edits within the YXXQ domain of BLCAP were reported to produce edited isoforms that induce STAT3 and activate JAK-STAT signalling in cervical cancer. On the other hand, reduced ADAR2-mediated RNA editing of BLCAP was shown in bladder cancer, astrocytoma and colorectal cancer]		Hepatocellular carcinoma	increased editing	[122]	Cell lines, mouse (xenografts)
			Bladder cancer	reduced ADAR2-mediated A-to-I RNA editing	[99]
			Astrocytoma	reduced ADAR2-mediated A-to-I editing	[99]
			Colorectal cancer	reduced ADAR2-mediated A-to-I RNA editing	[99]
			Cervical cancer	multiple A-to-I RNA editing (ADAR1-mediated) within the YXXQ domain	[98]	Cell lines
GluR-B	Reduced editing of GRIA2 leads to production of unedited isoforms of GluA2 subunits that confer increased Ca2+-permeability on brain AMPA receptors containing them. This causes higher intracellular calcium concentration which activates the Akt pathway and as a consequence induces cell proliferation. [In a healthy brain, GRIA2 is edited at >99.9%. This makes the AMPA receptor channel nearly impermeable to calcium ions. Impermeable AMPA receptor channel inhibits cell migration and induces apoptosis]	Q607R	Malignant glioma	reduced ADAR2-mediated A-to-I RNA editing	[102]	Cell lines, mouse
CDC14B	Reduced CDC14B editing causes its decreased expression, which results in degradation of p21 and p27 and thus, increased tumour progression and aggressiveness. [Editing causes increased expression of CDC14B which promotes Skp2 degradation. This prevents ubiquitination and degradation of p21 and p27 tumour suppressor proteins, leading to inhibition of cell proliferation]		Astrocytoma	decreased ADAR2-mediated RNA editing	[104]	Cell lines, mouse
PTPN6	PTPN6 is a tumour suppressor which inhibits different growth-promoting receptors, including the c-Kit tyrosine kinase. [Editing in PTPN6 transcript results in production of non-functional PTPN6 protein]	intron retention	Acute myeloid leukaemia (AML)	multiple A-to-I RNA editing, mainly at the intronic putative branch site in myeloblasts	[90,154,155]	Cell lines, mouse
Cancer progression step: cancer survival and proliferation
PCA3	PCA3, is a long noncoding RNA transcribed in the antisense direction from within an intron of the protein-coding PRUNE2 (tumour suppressor gene). PCA3 negatively regulates PRUNE2 levels by forming a PRUNE2-PCA3 double stranded RNA which is then edited by ADAR1. [PRUNE2 decreases cell proliferation, but if edited in the PRUNE2-PCA3 dsRNA duplex and downregulated, the reduced PRUNE2 increases cancer cell proliferation and migration]	multiple sites	Prostate cancer	ADAR1-mediated A-to-I RNA editing	[105]	Cell lines, mouse (xenografts)
NF1	NF1 is a tumour-suppressor, a GTPase-activating protein which negatively regulates the RAS/MAPK pathway which is involved in cell cycle and cell division. [RNA editing in NF1 cause a nonsense mutation and can influence cellular growth control and neural development]	R1306*	Peripheral nerve sheath tumours (PNSTs)	C-to-U RNA editing	[109–111]	Cell lines
FLNB	FLNB (filamin B) is a protein involved in cellular cytoskeleton formation. [Editing in FLNB may lead to alterations of cell shape and mobility what may affect the risk of metastasis]	M2269V	Hepatocellular carcinoma, Oesophageal squamous cell carcinoma	increased A-to-I RNA editing level	[97,112]	Cell lines
RHOQ	RHOQ encodes the signalling protein RhoQ GTPase enzyme. Proteins of the Rho family promote reorganization of the actin cytoskeleton and regulate cell shape, attachment and motility. [The edited RHOQ isoform shows increased activity, enhancing reorganization of actin cytoskeleton, which may lead to cancer invasion]	N136S	Colorectal cancer	A-to-I RNA editing	[113]	Cell lines
IGFBP7	Reduced editing of IGFBP7 has been shown to inhibit programmed cell death and to promote tumorigenesis. [IGFBP7 is a pro-apoptotic protein. The edited IGFBP7 isoform prevents proteolytic cleavage by matriptase and this stabilized IGFBP7 induces apoptosis]	K95R	Oesophageal squamous cell carcinoma	reduced ADAR2-mediated A-to-I RNA editing	[114]	Cell lines, mouse (xenografts)
Cancer progression step: progression, metastasis
SLC22A3	SLC22A3 binds to ACTN4 (an actin-binding protein which promotes metastasis and formation of filopodia) and inhibits its activity. [The edited SLC22A3 isoform has reduced direct binding to ACTN4 and this increases ACTN4 activity which promotes metastasis]	N72D	Oesophageal squamous cell carcinoma	elevated ADAR2-mediated A-to-I RNA editing	[132]	Cell lines, mouse
FAK	Focal adhesion kinase (FAK), is a tumour metastasis promoting factor, which regulates cell migration by controlling the disassembly of focal adhesions. [RNA editing in FAK results in its increased expression and stabilization, which may promote cell migration and cell invasiveness]	RNA editing of intron 26	Non-small cell lung cancer	ADAR1-mediated A-to-I RNA editing	[134]	Cell lines
PODXL	PODXL is an oncogenic protein that stimulates cancer cell migration and invasiveness by its interaction with actin-binding protein EZR. The unedited isoform of PODXL was found to promote tumour progression. [RNA editing in PODXL leads to a loss-of-function phenotype that reduces growth and invasiveness of cancer cells]	H241R	Gastric cancer	no A-to-I RNA editing in this transcript due to loss of ADAR2 leads to tumour progression	[144]	Cell lines and mice (xenografts)
GABRA3	The unedited isoform of GABRA3 activates the Akt pathway in breast cancer and thereby promotes cell migration and metastasis. [The edited GABRA3 has an opposing function to unedited GABRA3]	I342M	Breast cancer	reduced ADAR1-mediated A-to-I RNA editing	[130]	Cell lines and mice
COPA	COPA encodes coatomer subunit alpha which is a part of the non-clathrin-coated vesicular coat proteins (COPs) complex. This complex mediates protein transport between the endoplasmic reticulum (ER) and Golgi compartments. [Reduced RNA editing at the COPA I164V site promotes liver metastasis in colorectal cancer and is also observed in hepatocellular carcinoma]	I164V	Hepatocellular carcinoma	reduced ADAR2-mediated RNA editing	[112,145]	Cell lines, mice
			Colorectal cancer	reduced ADAR2-mediated A-to-I RNA editing promotes liver metastasis in colorectal cancer	[133]	Cell lines
DHFR	DHFR is a dihydrofolate reductase which plays a role in folate metabolism and is targeted by methotrexate (a chemotherapeutic that blocks the action of folic acid). [The edited transcript of DHFR is resistant to specific microRNAs (miR25-3p and miR125a-3p) and this resistance stabilizes it. Higher cellular levels of edited DHFR protein cause resistance to chemotherapy with methotrexate, thus promoting cells growth]		Breast cancer	ADAR1-mediated A-to-I RNA editing	[131]	Cell lines
Cancer progression step: progression, metastasis
CDK13	CKD13 is a cyclin-dependent kinase which participates in pre-mRNA splicing [The edited sites change residues in the N-terminal region of CDK13, the conformation of which is crucial for interacting with p32 (a regulating partner of the ASF/SF2 splicing factor)]	Q103R, K96R	Hepatocellular carcinoma	ADAR1-mediated, increased A-to-I RNA editing level	[156]	Cell lines