Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions

Table 1 MicroRNAs reduced by DNA methylation in Helicobacter pylori infection

MicroRNA	Targets	Consequences/associations
miR-210	STMN1	Aberrant proliferation
	DIMT1	Increased H. pylori content, atrophy and neutrophil and mononuclear infiltration
miR-375	MDM2	p53 inhibition
	JAK1/STAT3	JAK1/STAT3 activation and neoplastic transformation
	14-3-3	Bcl binding and cell survival
	PDK1	PI3K/Akt pathway
miR-124	CDK6	Cell cycle progression
Let-7a	c-myc and DNMT3B	Ras pathway activation
miR-34	Bcl-2	Apoptosis inhibition
miR-10b	MAPs	Microtubule-associated protein oncogene
miR-185	DNMT1 and EZH2	Proliferation and EMT
		LNM and poorer prognosis
miR-490-3p	Cyclin B1	EMT; proliferation; colony formation; migration; invasion
	SMARCD1	Metastasis and poorer survival
		Decreased through the spectrum of gastric carcinogenesis

STMN1: Stathmin/oncoprotein 18; DIMT1: DIM1 dimethyladenosine transferase 1 homolog (S. cerevesiae); MDM2: Mouse double minute 2 homolog/E3 ubiquitin-protein ligase Mdm2; JAK1: Janus kinase 1; STAT3: Signal transducer and activator of transcription 3; PDK1: Phosphoinositide-dependent kinase-1; CDK6: Cyclin-dependent kinase 6; DNMT3B: DNA (cytosine-5-)-methyltransferase 3 beta; Bcl-2: B-cell lymphoma 2; MAPs: Microtubule-associated proteins; DNMT1: DNA (cytosine-5)-methyltransferase 1; EZH2: Enhancer of zeste homolog 2; EMT: Epithelial-mesenchymal transition; LNM: Lymph node metastasis; SMARCD1: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1.

Table 2 Potential oncogenic microRNAs

MicroRNA	H. pylori	GC	Targets	Consequences/associations
miR-21	↑	↑	RECK	Decreased apoptosis; cell proliferation, invasion
			PTEN	MMP stimulation
			ABP	PI3K/Akt signaling pathway activation
miR-106a			RB1	E2F transcription; lymphatic and distant metastasis
miR-584	↑		Foxa1	EMT promotion; decreased E-cadherin
miR-1290			SMAD2	Cell differentiation and remodeling; IM development
miR-296-5p		↑	CDX1	Erk1/2 activation; growth promotion
miR-222	↑	↑	RECK	Proliferation
miR-223	↑	↑	EPB41L3	Migration and invasion
miR-106b-25 cluster		↑	p21CIP1/WAF1	Decreased response to TGF-Β
			Bim	Cell cycle progression; inhibition of apoptosis
			E2F1
miR-130b		↑	RUNX3|Bim	Proliferation (CDK2 activation) and invasion
miR-301a			RUNX3	Apoptosis inhibition
miR-181b	↑	↑	Timp3	Inhibition of apoptosis, cell proliferation, invasion and migration
miR-27a	↑	↑	FoxO1	Increased oxidative stress
			Prohibitin

H. pylori: Helicobacter pylori; GC: Gastric cancer; RECK: Reversion-inducing cysteine-rich protein with Kazal motifs; PTEN: Phosphatase and tensin homolog; ABP: Androgen-binding protein; MMP: Matrix metalloproteinase; PI3K: Phosphoinositide 3-kinase; E2F: E2F family; Foxa1: Forkhead box protein A1; SMAD2: Mothers against decapentaplegic homolog 2; EMT: Epithelial-mesenchymal transition; IM: Intestinal metaplasia; CDX1: Caudal type homeobox 1; Erk: Extracellular-signal-regulated kinases; EPB41L3: Erythrocyte membrane protein band 4.1-like 3; p21: Cyclin-dependent kinase inhibitor 1; Bim: Bim gene (Bcl-2 family member); TGF-Β: Transforming growth factor beta; RUNX3: Runt-related transcription factor 3; Timp3: TIMP Metallopeptidase Inhibitor 3; FoxO1: Forkhead box protein O1.

Table 3 Potential tumor suppressor microRNAs

MicroRNA	H. pylori	GC	Targets	Consequences/associations
miR-185	↓		DNMT1 and EZH2	DNA methylation; proliferation; EMT; LNM; poor prognosis
miR-204	↓		SIRT1	EMT; invasion
miR-106b	↓			Proliferation (TGF-Β induced cell cycle arrest suppression)
miR-320	↓	↓	Mcl-1	Apoptosis inhibition; progression of prenoplastic conditions
				Relapse of tumors; chemoterapeutic resistance
miR-101,	↓	↓	Mcl-1	Apoptosis inhibition
miR-515-5p			SOC2; DNMT1	Let-7 attenuation
miR-490-3p	↓	↓	Cyclin B1	EMT; proliferation; colony formation; migration; invasion
			SMARCD1	Metastasis and poorer survival
				Decreased through the spectrum of gastric carcinogenesis
miR-370	↓	↓	FoxM1	↓p27 expression; cell cycle progression and proliferation
				Decreased through the spectrum of gastric carcinogenesis
miR-328	↓		CD44v9	Survival and proliferation of metaplastic cells
Let-7	↓	↓	Ras	Cell proliferation and colony formation
			c-myc
			HMGA2	Migration and invasion
			Cthrc1
miR-200,	↓	↓	ZEB1/2	Epithelial differentiation; EMT suppression
miR-141,				Decreased E-cadherin, inhibition of migration and invasion
miR-429			Cyclin D1	Proliferation
			Bcl-2|XIAP	Apoptosis inhibition
				Tumor size, lymphatic invasion and LNM
miR-141	↓		FGFR2	Proliferation
miR-375	↓	↓	MDM2	p53 inactivation
			JAK2/STAT3	Neoplastic transformation; proliferation and migration
			3/3/2014	Inhibition of apoptosis
			PDK1	PI3K/Akt signaling pathway activation
miR-524-5p		↓	Jagged-1; Hes-1	Cell proliferation and invasion
miR-449	↓	↓	Cyclin E2|Met	Proliferation, angiogenesis, invasion and metastasis
			Gemini|SIRT1
miR-203	↓	↓	CASK	Cell growth, colony formation and cell invasion
miR-29a		↓	p42.3; Mcl-1	Cell cycle progression and proliferation
miR-29c
miR-15b, 16, 34, 181b, 497		↓	Bcl-2	Apoptosis inhibition
miR-218	↓	↓	ECOP	Activation of NF-κB and increased COX-2; apoptosis inhibition
			SLIT/ROBO1	Invasion and metastasis

H. pylori: Helicobacter pylori; GC: Gastric cancer; DNMT1: DNA (cytosine-5)-methyltransferase 1; EZH2: Enhancer of zeste homolog 2; EMT: Epithelial-mesenchymal transition; LNM: Lymph node metastasis; SIRT1: Sirtuin 1; TGF-Β: Transforming growth factor beta; Mcl1: Myeloid cell leukemia 1; SOC2: Suppressor of clear homolog; SMARCD1: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1; FoxM1: Forkhead box protein M1; HMGA2: High-mobility group AT-hook 2; Cthrc1: Collagen triple helix repeat containing 1; ZEB1/2: Zinc finger E-box binding homeobox 1/2; XIAP: X-linked inhibitor of apoptosis protein; FGFR2: Fibroblast growth factor receptor 2; MDM2: Mouse double minute 2 homolog; JAK1: Janus kinase 1; STAT3: Signal transducer and activator of transcription 3; PDK1: Phosphoinositide-dependent kinase-1; Hes-1: Hairy and enhancer of split-1; CASK: Calcium/calmodulin-dependent serine protein kinase; ECOP: EGFR-coamplified and overexpressed protein; NF-κB: Nuclear factor kappa B; COX-2: Cyclooxygenase-2.