Dysregulation of non-coding RNAs in gastric cancer

Table 1 MicroRNAs down-regulated in gastric cancer

ncRNA	Summary of findings/clinical relevance	q-PCR	Targets	Roles	Cases	Location	Ref.
miR-141	Reduced in metastasis positive tissues; Might be a prognostic marker and therapeutic target	√	TAZ	Proliferation, invasion and migration	36 GC vs paired adjacent tissues	China	[223]
miR-874	Reduced miR-874 promotes angiogenesis via STAT3; Might be a therapeutic target	√	STAT3	Tumor growth and angiogenesis	80 GC vs paired adjacent tissues	China	[187]
miR-101	Lower level parallels with EZH2 overexpression	√	EZH2	E-cadherin dysfunction	37 GC vs 5 normal gastric mucosa	Portugal	[224]
miR-103a	Tumor suppressor by targeting c-Myb	√	c-Myb	Proliferation, invasion and migration	80 GC vs paired adjacent tissues	China	[225]
miR-335	Can be silenced by promoter hypermethylation which might be a predictive epigenetic marker and a therapeutic strategy	√	RASA1	Invasion and metastasis	15 GC vs paired adjacent tissues	China	[52]
miR-335	Could be a therapeutic target for GC therapies and a prognostic factor	√	Bcl-w, SP1	Proliferation, invasion and metastasis	70 GC vs paired adjacent tissues	China	[226]
let-7a	A potential target for diagnosis and therapy	√	RAB40C	Proliferation and colony formation	27 GC vs paired adjacent tissues	China	[227]
miR-490-3p	Reduced miR-490-3p reactivates SMARCD1 to confer malignant phenotypes	√	SMARCD1	Growth and metastasis	14 GC vs 15 normal gastric tissues	Hong Kong	[228]
miR-200c/141	Reduced miRNA decreases ZEB1/2 expression and increases E-cadherin expression	√	ZEB1/2	Invasion and migration	64 GC vs paired adjacent tissues	China	[229]
miR-200b /c	Might be a marker of prognosis and therapeutic target	√	DNMT3A, DNMT3B, SP1	Proliferation, invasion and migration	36 GC vs paired adjacent tissues	China	[230]
miR-200	Down-regulated miR-200 reduced E-cadherin expression, playing a role in the carcinogenesis of EBV-associated GC	√	ZEB1, ZEB2	Cell-to-cell adhesion and migration	36 GC vs paired adjacent tissues (EBV-associated and EBV-negative)	Japan	[231]
miR-204-5p	Restoration of miR-204-5p might provide a therapeutic strategy for GC	√	USP47, RAB22A	Proliferation	102 GC vs paired adjacent tissues	China	[232]
miR-367	A key negative regulator of invasion and metastasis of GC; Might be a therapeutic target	√	Rab23	Invasion and migration	37 GC vs paired adjacent tissues	China	[233]
miR-328	MiR-328-mediated CD44 overexpression may associate with the carcinogenesis of GC	√	CD44v9	Survival and proliferation of metaplastic cells	54 patients underwent gastric resection without preoperative treatment	Japan	[181]
miR-328	Macrophages mediated miR-328-CD44 signaling may be a therapeutic target for gastrointestinal cancer	√	CD44	Cell growth and drug resistance	63 GC vs paired adjacent tissues	Japan	[234]
miR-495	A tumor suppressor and potential therapeutic target for GC peritoneal metastasis	√	PRL-3	Invasion and metastasis	20 GC vs 10 normal gastric tissues	China	[53]
miR-551a	A tumor suppressor targeting PRL-3 oncogene to inhibit GC cell migration and invasion	√	PRL-3	Invasion and migration	30 malignant vs 4 normal gastric tissues	China	[235]
miR-133b	A potential diagnostic marker and therapeutic target	√	FSCN1	Proliferation, invasion and migration	100 GC vs paired adjacent tissues	China	[236]
miR-542-3p	A tumor suppressor and a potential therapeutic target	√	AEG-1	Cell growth	22 GC vs paired adjacent tissues	China	[112]
miR-126	Suppresses tumor growth and angiogenesis through targeting VEGF-A; A potential therapeutic target	√	VEGF-A	Tumori-genicity and angiogenesis	68 GC vs paired adjacent tissues	China	[119]
miR-126	May function as a tumor suppressor in GC	√	Crk	Proliferation, cell cycle, apoptosis, invasion and migration	60 GC vs paired adjacent tissues	China	[237]
miR-29s	Increasing the expression of miR-29s may be a therapeutic strategy for GC	√	AKT2	Invasion	20 GC vs paired adjacent tissues	China	[120]
miR-29c	Reduced miR-29c expression is an early event in GC development; Potential diagnostic and therapeutic biomarkers	√	ITGB1	Proliferation, adhesion, invasion and migration	274 GC vs paired adjacent tissues	South Korea, Japan, United States	[215]
miR-29 family	Might be potential prognostic markers and therapeutic targets	√	CCND2, MMP-2	Proliferation apoptosis and invasion	115 GC vs paired adjacent tissues	China	[238]
miR-29c	Might be a tumor suppressor	√	RCC2	Proliferation and colony formation	12 GC vs paired adjacent tissues	Japan	[239]
miR-193b	Might be a potential prognostic marker	√	Unknown	Differentiation and survival	48 GC vs paired adjacent tissues	China	[240]
miR-203	Might be a therapeutic target for H. pylori infection induced GC	√	CASK	Proliferation and invasion	50 pairs of H. pylori positive and negative gastric tissues	China	[241]
miR-210	Epigenetic silencing of miR-210 involves in chronic H. pylori infection associated GC	√	STMN1, DIMT1	Proliferation	20 GC vs paired adjacent tissues	Japan	[242]
miR-34 family	Plays a role in the control of GC development	√	Yin Yang 1	Growth, colony formation, migration, invasion, and tumorsphere formation	32 GC vs paired adjacent tissues	Taiwan	[243]
miR-34b and	Down-regulated by hypermethylation of upstream CpG islands indicating a poor clinical outcome	√	Unknown	Unknown	72 GC vs paired adjacent tissues	Taiwan	[244]
miR-129-3p
miR-24	A novel tumor suppressor and a potential therapeutic target	√	RegIV	Proliferation, invasion and migration	63 GC vs paired adjacent tissues	China	[245]
miR-185	Regulating the sensitivity of GC to chemotherapy	√	ARC	Chemotherapeutic sensitivity	25 GC vs paired adjacent tissues	China	[246]
miR-1207-5p and miR-1266	hTERT suppressors in GC and potential therapeutic targets	√	hTERT	Cell growth, cell cycle and invasion	58 GC vs adjacent tissues	China	[108]
miR-365	Playing a role in tumorigenesis; A potential therapeutic target	√	Cyclin D1, cdc25A	Proliferation and colony formation	127 GC vs paired adjacent tissues	China	[105]
miR-760	A potential prognostic predictor and therapeutic target	√	Histone mRNA	Unknown	53 bone marrow samples from stage IV patients vs 52 stage I patients; 22 stage IV GC vs 29 stage I GS tissues	Japan	[247]
miR-143/145	DDX6 contributes to the control of NCR143/145 RNA stability in P-bodies and post-transcriptionally regulated miR-143/145 expression	√	Unknown	Cell survival, proliferation and malignant transformation	14 GC tissues vs paired adjacent tissues	Japan	[84]
miR-206	A potential tumor suppressor and therapeutic target	√	CyclinD2	Proliferation, cell cycle and tumor growth	30 primary GC vs paired distant tissues	China	[248]
miR-204	A potential target for preventive and therapeutic strategies	√	Bcl-2	Migration, colony forming and chemotherapy resistance	92 gastric tumor specimens vs paired adjacent tissues	Italy	[249]
miR-124	A tumor suppressor; Play a role in miRNA-mediated SPHK1 expression	√	SPHK1	Proliferation and tumourigenicity	20 GC vs paired adjacent tissues	China	[117]
miR-409-3p	A tumor suppressor involving the direct targeting and inhibition of PHF10	√	PHF10	Proliferation and apoptosis	67 GC vs paired adjacent tissues	China	[250]
miR-409-3p	Suppresses GC invasion and metastasis by directly targeting RDX; Reduced miR-409-3p is prone to lymph node metastasis	√	RDX	Invasion and migration	90 GC vs paired adjacent tissues	China	[251]
miR-148a	Reduced miR-148a contributes to GC lymph node-metastasis and progression; A potential therapeutic target for GC metastasis	√	ROCK1	Invasion, migration and metastasis	90 GC vs paired normal tissues	China	[252]
miR-148b	A potential biomarker and therapeutic target	√	CCKBR	Proliferation and tumorigenicity	106 GC vs paired adjacent tissues	China	[253]
miR-449	A member of the miR-34 family playing an important role in GC	√	GMNN, MET, CCNE2, SIRT1	Cell cycle, proliferation and induce senescence	10 GC vs paired adjacent tissues	Denmark	[254]
miR-486	A tumor-suppressor; Associated with the direct targeting and inhibition of OLFM4	√	OLFM4	Proliferation, invasion and migration	29 GC vs paired adjacent tissues	Singapore	[255]
miR-142-5p	A potential predictor of progression and predict recurrence risk for GC	√	MAPK, Wnt, VEGF	Recurrence risk related	65 GC samples	China	[256]
miR-125a-5p	Reduced miR-125a-5p is associated with enhanced malignant potential; A potential prognostic marker	√	ERBB2	Proliferation	87 GC samples	Japan	[257]
miR-516a-3p	An anti-metastamir with therapeutic potential in blocking metastatic dissemination of GC	√	SULF1	Proliferation, invasion and migration	8 normal stomach tissues, 12 GC tissues from the patients with peritoneal dissemination and 12 GC tissues without peritoneal dissemination	Japan	[258]
miR-181c	Silenced through methylation playing important roles in gastric carcinogenesis	√	NOTCH4, and KRAS	Proliferation	16 GC surgical specimens vs paired non-cancerous counterparts	Japan	[259]
miR-212	Reduced miR-212 may be related to gastric carcinogenesis	√	MECP2	Proliferation	11 GC vs paired adjacent tissues	Japan	[260]
miR-338-3p	MiR-338-3p inhibits the EMT progression in GC cells by targeting ZEB2 and MACC1/Met/Akt pathway	√	ZEB2, MACC1	Invasion and migration	20 GC vs paired adjacent tissues	China	[261]
miR-217	A potential prognostic marker; miR-217-EZH2 axis may be a potential therapeutic target	√	EZH2	Proliferation, invasion and migration	83 GC tissues vs adjacent tissues	China, United States	[262]
miR-15a and miR-16-1	MiR-15a and miR-16-1 have inhibitory effect providing a therapeutic potential in GC	√	YAP1	Proliferation, colony formation, invasion and migration	60 GC vs paired adjacent tissues	Hong Kong	[263]

GC: Gastric cancer.

Table 2 MicroRNAs up-regulated in gastric cancer

ncRNA	Summary of findings/clinical relevance	q-PCR	Targets	Roles	Cases	Location	Ref.
miR-23a/b	Implicated in the progression of GC. A potential prognosis marker	√	Unknown	Unknown	160 GC vs adjacent tissues	China	[264]
miR-500	Highly correlated with malignant progression and poor survival of GC	√	CYLD, TAX1BP1, OTUD7B	Proliferation, survival and tumorigenicity	10 GC vs adjacent tissues	China	[137]
miR-374a	A promising therapeutic target	√	SRCIN1	Proliferation, tumor growth migration and invasion	18 GC tissues vs adjacent tissues	China	[265]
miR-199a-3p	A tumor promoter in GC targeting and inhibition of ZHX1; A potential target for GC prevention and therapy	√	ZHX1	Proliferation and apoptosis	52 GC vs adjacent tissues	China	[266]
miR-18a	A potential marker for risk stratification in the management of GC patients	√	PIAS3, STAT3	Unknown	82 patients with GC and 65 healthy controls (plasma)	China	[204]
miR-196a	A potential prognostic marker in GC	√	Unknown	Differentiation and survival	48 GC vs adjacent tissues	China	[240]
miR-223, miR-16, miR-100	Up-regulated in serum implicates their potential diagnostic value; Significantly elevated expression of the three miRNAs in advanced GC patients suggests their availability in cancer staging	√	PIAS3	Unknown	50 GC patients and 47 healthy controls (serum)	China	[202]
miR-135a-5p	Play a role in miRNA-135a-5p-AP-2α-BCL-2 pathway providing therapeutic potential for GC and solution for insensitivity of GC to chemotherapy	√	AP-2α	Cell resistance to apoptosis, sensitivity to adriamycin	20 GC vs adjacent tissues	China	[267]
miR-199a-5p	SRF/miR-199a-5p/E-cadherin pathway promotes GC EMT and metastasis; A potential therapeutic target or biomarker for GC progression	√	E-cadherin	Adhesion, invasion, and metastasis	7 GC vs pairs adjacent tissues	China	[268]
miR-25	A potential biomarker for the prognosis of GC	√	ERBB2, 1(TOB1)	Migration, invasion and proliferation	33 GC vs paired adjacent tissues	China	[269]
miR-942	A potential drug response biomarker and therapeutic target for TRAIL resistant tumors	√	ISG12a	Apoptosis	28 GC tissues	China	[134]
miR-196a/b	A potential therapeutic target in suppressing GC metastasis	√	Radixin	Metastasis	109 GC vs paired adjacent tissues	Taiwan	[172]
miR-19a/b	A member of miR-19a/b facilitating GC cell migration, invasion and metastasis, implicating a novel mechanism for the malignant phenotypes of GC	√	MXD1	Migration and invasion	141 GC vs paired adjacent tissues	China	[173]
miR-423-5p	A potential therapeutic target	√	TFF1	Proliferation and invasion	15 GC vs paired adjacent tissues	China	[270]
miR-183-96-182 cluster	A novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-catenin/TCF/ LEF-1 pathway in GC	√	FoxO1	Proliferation and migration	8 GC vs paired adjacent tissues	United States	[83]
miR-215	Influencing cell proliferation by targeting RB1	√	RB1	Proliferation	51 GC vs paired adjacent tissues	China	[271]
miR-17-92 cluster	Cluster including miR-19b, miR-20a and miR-92a associates with the development of GC stem cells; and miR-92a as a potential predictive prognostic marker for miR-92a in GC	√	E2F1, HIPK1	Self-renewal and proliferation	97 GC specimens	China	[272]
miR-296-5p	MiR-296-5p-CDX1-ERK1/2 axis play a role in gastric tumorigenesis; A potential therapeutic target	√	CDX1	Proliferation	16 GC vs paired adjacent tissues	China	[273]
miR-181a	Associated with increased risk and poor survival of GC	√	MTMR3	Unknown	50 GC vs paired adjacent tissues	China	[274]
miR-196a	Contributing to gastric carcinogenesis; A potential therapeutic target and prognostic factor	√	p27	Proliferation, apoptosis and tumorigenesis	36 GC vs paired adjacent tissues	China	[275]
miR-196b	Transcriptionally regulated by ETS2; A potential diagnostic marker and therapeutic target	√	AnnexinA1, HOXB8	Migration and invasion	63 GC vs paired adjacent tissues	Taiwan	[276]
miR-378	Up-regulated in serum while down-regulated in GC tissues. A potential serum biomarker in GC detection	√	Unknown	Unknown	4 GC vs paired adjacent tissues, 40 GC serum samples vs 41 healthy controls	China	[277]
miR-370	Associated with GC progression by targeting TGFβ-RII	√	TGFβ-RII	Migration	33 GC vs adjacent tissues	Taiwan	[278]
miR-192 miR-215	Exerting cell growth and migration-promoting effects	√	ALCAM	Migration, invasion, proliferation, cell cycle and apoptosis	31 non-neoplastic stomach tissues and 25 GC tissues	United States	[279]
miR-200b	A potential diagnostic and prognostic biomarker; A potential therapeutic target for peritoneal dissemination	√	Unknown	Migration and invasion	173 GC vs paired normal gastric epithelium tissues	Japan	[280]

GC: Gastric cancer.

Table 3 MicroRNAs up-regulated or down-regulated in gastric cancer

ncRNA	Summary of findings/clinical relevance	q-PCR	Targets	Roles	Cases	Location	Ref.
miR-183 ↑	A potential biomarker for GC progression and therapeutic target	√	PDCD4	Proliferation, migration, invasion, and apoptosis	80 GC vs 20 non-tumorous gastric mucosa tissues	China	[131]
miR-183 ↓	A tumor suppressor partially through regulation of Ezrin; A potential therapeutic target	√	Ezrin	Invasion	52 pairs of paraffin-embedded GC and adjacent tissues; 5 fresh tissues samples from three patients	China	[281]
miR-146a ↑	A key factor in the regulation of NF-κB activity	√	CARD10, COPS8	Inhibits NF-κB activation	37 GC vs paired adjacent tissues	Denmark	[282]
miR-146a/b ↓	MiR-146a/b/UHRF1 axis associates with the GC metastasis; A potential therapeutic target in blocking GC metastasis	√	UHRF1	Invasion and metastasis	15 primary GC tissues compared with matched adjacent normal tissues	China	[180]
miR-146a ↓	MiR-146a/WASF2 axis may associate with the migration and invasion of GC cells; A potential therapeutic target	√	WASF2	Invasion and metastasis	20 GC vs paired adjacent tissues	China	[283]
miR-146a ↓	Targeting EGFR and IRAK1; A potential prognostic factor	√	EGFR, IRAK1	Invasion and metastasis	90 GC vs paired adjacent tissues	Japan	[179]
miR-9 ↑	Targeting and suppressing CDX2 expression promote GC cell proliferation	√	CDX2	Proliferation	27 GC tissues	Japan	[284]
miR-9 ↓	Ectopic expression of miR-9 inhibits the proliferation, migration and invasion of GC cells	√	MMP2, MMP9, Twist, N-cadherin	Invasion and metastasis	72 GC vs adjacent tissues	Taiwan	[285]
miR-9 ↓	A tumor suppressor targeting NF-κB1	√	NF-κB1	Proliferation	9 GC vs paired adjacent tissues	China	[286]
miR-375 ↑	A predictor of GC; progression and recurrence risk for GC patients	√	P53, MAPK, Wnt, VEGF	High frequency recurrence and poor survival	34 frozen fresh tissues and 38 paraffin-embedded tissues	China	[256]
miR-375 ↓	A tumor suppressor; Playing a role in gastric tumorigenesis	√	JAK2	Proliferation	48 GC vs paired adjacent tissues	China	[287]
miR-375 ↓	A tumor suppressor	√	PDK1, 14-3-3zeta	Apoptosis, proliferation	22 samples from GC and 5 normal control tissues	Japan	[288]
miR-218-5p ↑	MiR-218-5p targets and suppresses TFF1 and influences the progression of GC in an Erk1/2-dependent manner; A potential therapeutic target	√	TFF1	Proliferation	42 GC vs paired adjacent tissues	China	[289]
miR-218 ↓	Disruption of Slit-miR-218-Robo1 regulatory circuit may contribute to GC metastasis. A potential therapeutic target in blocking GC metastasis	√	Robo1	Invasion and metastasis	40 GC vs paired adjacent tissues	China	[290]

GC: Gastric cancer.