Gastric cancer: An epigenetic view

Table 1 Important miRNAs and their targets and biological functions in gastric cancer

miRNAs	Expression	Targets	Functions	Ref.
miR-21	Up	EMT	Tumor growth, metastasis	[89]
miR-183	Up	UVRAG	Cell proliferation, autophagy, apoptosis	[90]
miR-765	Up	BATF2	Chemosensitivity	[91]
miR-155	Up	TP53INP1	Cell cycle, proliferation, migration	[92]
miR-130b	Up	NFκB, p65	Cell proliferation, tumorigenesis	[93]
miR-92a-1-5p	Up	FOXD1	Metaplasia	[94]
miR-135b	Up	FOXN3/RECK	Cell invasion, CSC-like properties	[95]
miR-181a-5p	Up	AKT3	Cell proliferation, apoptosis, tumor growth	[96]
miR-224	Up	PAK4	Cell proliferation, migration	[97]
let-7i	Down	COL1A1	Cell invasion, metastasis	[98]
miR-146a	Down	-	Cell migration	[99]
MiR-12129	Down	SIRT1	Cell cycle, proliferation	[100]
miR-27b	Down	NR2F2	cell proliferation, tumor growth	[101]
miR-140-5p	Down	NOTCH1	Cell proliferation, migration, apoptosis	[102]
miR-34a	Down	Snail	Cell proliferation, invasion	[103]
miR-9	Down	TNFAIP8L3	Cell proliferation, migration	[104]
miR-195	Down	HMGB1	Chemosensitivity	[105]

Table 2 Important lncRNAs and their targets and biological functions in gastric cancer

LncRNAs	Expression	Targets		Functions	Ref.
MIAT	Up		miR-29a-3p/HDAC4	Cell proliferation, migration and invasion	[106]
PANDAR	Up		CDKN1A	Tumor growth	[107]
FOXD2-AS1	Up		EphB3	Tumorigenesis	[108]
SMARCC2	Up		miR-551b-3p/TMPRSS4	Cell proliferation, migration	[109]
H19	Up		miR-519d-p/LDHA	Aerobic glycolysis, proliferation, and immune escape	[110]
TINCR	Up		STAU1/CDKN2B	Cell proliferation, cell cycle	[111]
CCAT2	Up		E-cadherin, LATS2	Cell proliferation, invasion	[112]
AOC4P	Up		Vimentin, MMP9	Cell proliferation, migration, invasion	[113]
CTC-497E21.4	Up		miR-22-3p/NET1	Cell cycle, proliferation, invasion	[114]
BANCR	Up		ERK1/2, NF-κB1	Cell proliferation, apoptosis, chemosensitivity	[115,116]
HOTTIP	Up		miR-216a-5p, miR-615-3p	Chemosensitivity, cell proliferation, apoptosis	[117,118]
AC100830.4, CTC-501O10.1, RP11-210K20.5	Up		-	Differentially expressed in GC and normal tissue	[119]
INHBA-AS1, CEBPA-AS1, AK001058	Up		-	Differentially expressed in GC and normal tissue	[120]
CYTOP	Up		miR-103/RAB10	Cell proliferation, migration, apoptosis	[121]
NKX2-1-AS1	Up		SERPINE1/VEGFR-2	Cell proliferation, angiogenesis	[122]
NEAT1	Up		miR-17-5p/TGFβR2	Angiogenesis	[123]
ZFAS1	Up		EPAS1	Recurrence, metastasis	[124]
TSPEAR-AS2	Up		EZH2/GJA1, miR-1207-5p/CLDN4	Tumor progression	[125]
TMEM92-AS1	Up		YBX1/CCL5	Tumor progression	[126]
CRNDE	Down		NEDD4-1/PTEN	Chemosensitivity	[127]
MEG3	Down		miR-181a-5p/ ATP4B	Cell proliferation, migration, apoptosis	[128]
PCSK2-2:1	Down		-	Differentially expressed in GC and normal tissue	[129]
GNAQ-6:1	Down		-	Differentially expressed in GC and normal tissue	[130]
CTSLP4	Down		Hsp90α/HNRNPAB	Cell migration, invasion, EMT	[131]

Table 3 Important circRNAs and their targets and biological functions in gastric cancer

circRNAs	Expression	Targets	Functions	Ref.
circFAM73A	Up	miR-490-3p/ HMGA2	Cell proliferation, migration, CSC-like properties, chemosensitivity	[132]
circAFF2	Up	miR-6894-5p/ANTXR1	Cell proliferation, migration, invasion	[133]
circHIPK3	Up	miR-637 /AKT1	Tumorigenesis	[134]
circVAPA	Up	miR-125b-5p/STAT3	Chemosensitivity	[135]
circMAP7D1	Up	HER2	Cell proliferation, apoptosis	[136]
circ_0006282	Up	miR-144-5p/YWHAB	Cell proliferation, metastasis	[137]
circ_0081146	Up	miR-144/ HMGB1	Cell growth, migration, invasion	[138]
circ_SMAD4	Up	miR-1276/ CTNNB1	Tumorigenesis	[139]
circNEK9	Up	miR-409-3p/MAP7	Cell proliferation, migration, invasion	[140]
circ_0004104	Up	miR-539-3p/RNF2	Cell proliferation, metastasis, glutaminolysis	[141]
circPVT1	Up	miR-152-3p	Chemosensitivity	[142]
hsa_circ_0023409	Up	miR-542-3p/ IRS4	Cell proliferation, metastasis	[143]
circ_0044516	Up	miR-149-5p/HuR	Cell proliferation, migration, invasion, tumor growth	[144]
circLMO7	Up	miR-30a-3p/ WNT2	Cell growth, metastasis	[145]
hsa_circ_0001829	Up	miR-155-5p/SMAD2	Cell growth, metastasis	[146]
circCUL3	Up	miR-515-5p/STAT3/HK2	Cell proliferation, glucose consumption, lactate production, ATP quantity	[147]
circTMEM87A	Up	miR-142-5p/ULK1	Cell proliferation, metastasis	[148]
circPTPN22	Down	EMT	Cell proliferation, migration, EMT, invasion	[149]
hsa_circ_0004872	Down	miR-224/Smad4/ADAR1	Cell proliferation, migration, invasion, tumor growth, metastasis	[150]
hsa_circRNA_0009172	Down	miR-485-3p/NTRK3	Cell proliferation, migration, invasion, tumor growth	[151]
circ_002059	Down	miR-182/ MTSS1	Cell proliferation, migration	[152]
circ-ITCH	Down	miR-199a-5p/ Klotho	Metastasis	[153]
circCUL2	Down	miR-142-3p/ ROCK2	Cell transformation, chemosensitivity, tumorigenesis	[154]

Table 4 Examples of biomarkers in gastric cancer

Genes	Purpose	Findings	Ref.
RUNX3	Diagnosis/prognosis	Methylation status correlates with liver metastasis	[155]
MLH1	Diagnosis/prognosis	Methylation status correlates with tumor stage	[156]
RASSF1A	Diagnosis/prognosis	Methylation status correlates with advanced stage, and lymph node positivity	[157]
MGMT	Diagnosis/prognosis	Methylation status correlates with distant metastasis	[156]
ANOS1	Diagnosis	Expression correlates with tumor progression	[158]
RPRML	Prognosis	Expression correlates with survival	[159]
CTD-2510F5.4	Diagnosis/prognosis	Expression correlates with clinicopathological classification and survival	[160]
lncRNA-GC1	Diagnosis	Circulating exosomal level correlates with early detection and disease progression	[161]
mesothelin	Diagnosis	Expression correlates with Peritoneal Recurrence	[162]
MiR-379-5pMiR-410-3p	Prognosis	Expression correlates with metastasis	[163]
S100A9	Diagnosis /Prognosis	Expression correlates with tumor aggressiveness	[164]
Notch1/2/3/4	Prognosis	Expression correlates with immune infiltration	[165]
KAT2A	Diagnosis	Expression correlates with depth of tumor invasion and tumor stage	[166]

Table 5 Examples of epigenetic drugs in gastric cancer

Drugs	Targets	Status	Ref.
Clinical
Vorinostat + capecitabine + cisplatin	HDAC	Completed phase II test	[167]
Vorinostat + folinic acid+ 5‑fluorouracil+ irinotecan	HDAC	Completed phase I test	[168]
Azacytidine + epirubicin/oxaliplatin/capecitabine	DNMT	Completed phase I test	[169]
Cholecalciferol + HDACi	HDAC	Induce apoptosis in GC cells; Prevent bone loss in preliminary trials;	[170,171]
Preclinical
SAHA	HDAC	Suppress proliferation, induce apoptosis, chemosensitivity in GC cells	[172,173]
LBH589	HDAC	Suppress proliferation, induce chemosensitivity	[174,175]
Resveratrol	HAT, HDAC	Suppress proliferation, invasion, tumorigenesis in GC cells	[176,177]
Curcumin	HAT, HDAC	Suppress viability, proliferation, migration, induce autophagy, apoptosis in GC cells	[178,179]
Quercetin	HAT, HDAC	Induce apoptosis, cell cycle arrest in GC cells	[180,181]
Garcinol	HAT, HDAC, SIRTUIN	Suppress oxidation, inflammation, tumorigenesis in GC cells	[182,183]
Sodium butyrate	HAT, HDAC	Induce apoptosis in GC cells	[184]
Tenovin 6	SIRTUIN	Induce apoptosis, autophagy in GC cells	[185]
DZNEP	HMT	Suppress proliferation, apoptosis, invasion, induce apoptosis in GC cells	[186,187]
GSK126	HMT	Suppress proliferation, cell cycle angiogenesis EMT, tumorigenesis in GC cells	[188,189]
Compound 26	Lysine demethylase	Suppress growth, migration, invasion in GC cells	[190]