Long non-coding RNAs involved in metastasis of gastric cancer

Table 1 Mechanistic analysis of long non-coding RNAs involved in gastric cancer metastasis and clinical correlations

LncRNA ID	Dysregulation	Upstream regulators	Downstream targets	Metastasis processes	Clinical correlation	Univariate analysis (HR 95%CI) P < 0.05		Multivariate analysis (HR 95%CI) P < 0.05		Ref.
						OS	DFS	OS	DFS
MALAT1	Up	JMJD1A	UPF1, Snail, N-cadherin, ZEB1, VE-cadherin/β-catenin complex, ERK/MMP, FAK/paxillin, EGFL7, miR-122	EMT, Angiopoiesis, VM	Lymphatic metastasis, distant metastasis, TNM stage	1.38 (1.03-1.85)	1.40 (1.01-1.94)			[14,17,23,89,90]
HOTAIR	Up		PCR2, miR-34a, c-MET, SNAIL1, CDH1, miR-152, HLA-G	EMT, immune escape	Lymphatic metastasis, distant metastasis, TNM stage					[73-75,77,91-93]
FRLnC	Up	FOXM1	Twist, TGFβ-1	EMT						[25]
UCA1	Up		TGFβ-1, GRK2/ERK/MMP9	EMT, degradation of the ECM	Lymphatic metastasis, TNM stage	3.909 (1.592-9.599)		2.917 (1.069-7.962)		[30,73]
ATB	Up	TGFβ-1	miR-200s, ZEB1	EMT				3.50 (1.73-7.44)		[26]
XIST	Up		miR-101	EMT	Lymphatic metastasis, distant metastasis, TNM stage					[27]
SNHG-6	Up		miR-101-3P, ZEB1	EMT	Lymphatic metastasis, distant metastasis, TNM stage					[28]
ZFAS1	Up		ZEB1, SNAIL, Slug, Twist	EMT	Lymphatic metastasis, TNM stage					[29]
LINC00152	Up			EMT	Lymphatic metastasis, TNM stage	2.162 (1.327-3.524)		1.659 (1.008-2.731)		[94]
HULC	Up			EMT	Lymphatic metastasis, distant metastasis, TNM stage					[35]
Linc00978	Up		TGFβ/SMAD,Twist1, Slug	EMT	Lymphatic metastasis, TNM stage					[32]
YAP1	Up		vimentin, β-catenin, E-cadherin	EMT	Lymphatic metastasis, distant metastasis, TNM stage					[33]
Linc00261	Down		Slug, GSK3β	EMT	Lymphatic, metastasis		0.494 (0.300-0.812)		0.551 (0.323-0.940)	[36]
Linc00675	Down		Vimentin	EMT						[40]
SPRY4-IT1	Down		Vimentin	EMT, epigenetic regulation	Lymphatic metastasis, distant metastasis, TNM stage	1.247 (1473-1.996)	2.223 (1.806-2.59)	0.818 (0.314-1.567)	1.741 (1.324-2477)	[43,95]
LEIGC	Down			EMT						[44]
GClnc1	Up		WDR5/KAT2, H3K4, H3K9, SOD2	Epigenetic regulation		2.21 (1.46-3.33)		1.93 (1.24-3.00)		[15]
LOC100130476	Down	DNMT1		Epigenetic regulation	Lymphatic metastasis, distant metastasis, TNM stage					[47]
AK058003	Up		SNCG	Epigenetic regulation, Hypoxia	Lymphatic metastasis, TNM stage					[56]
BC005927	Up	HIF-1α	BPHB4	Hypoxia	Lymphatic metastasis, TNM stage					[57]
SNHG15	Up		MMP2, MMP9	Degradation of the ECM	Lymphatic metastasis, TNM stage					[96]
FENDRR	Down		MMP2, MMP9	Degradation of the ECM	Lymphatic metastasis	0.539 (0.337-0.862)	0.563 (0.370-0.856)	0.569 (0.321-0.960)	0.555 (0.344-0.897)	[16]
BM742401	Down		MMP9	Degradation of the ECM						[53]
C21orF96	Up			Lymphangiogenesis, VM	Lymphatic metastasis, distant metastasis					[68]
LINC00052	Up		Wnt/β-catenin pathway		TNM stage					[97]
AA174084	Down									[80]
RMRP	Down				Lymphatic metastasis					[81]
SNHG1	Up				Lymphatic metastasis, TNM stage					[98]
SNHG5	Down				TNM stage					[99]
MSTO2P	Up		miR-335		Lymphatic metastasis, distant metastasis					[100]
ZEB1-AS1	Up		miR-335-5p		Lymphatic metastasis, TNM stage					[101]
PTENP1	Down		miR-106b, miR-93		Lymphatic metastasis, TNM stage					[102]
RP11-19P22.6-001	Down		Nitric oxide synthase 2 (NOS2)		Lymphatic metastasis, TNM stage					[103]
PCAT-1	Up				distant metastasis					[104]
HOXD-ASI	Up				Lymphatic metastasis, distant metastasis, TNM stage					[105]
CARLo-5	Up				Lymphatic metastasis, distant metastasis					[106]
LINC00673	Down				Lymphatic metastasis					[107]
LINC00982	Down				Lymphatic metastasis, TNM stage					[108]
HMlincRNA717	Down				distant metastasis					[109]
PVT1	Up				Lymphatic metastasis					[110]
GACAT3	Up	IL-6/STAT3			Distant metastasis, TNM stage					[111]
Sox2ot	Down				Distant metastasis	3.241 (1.239-6.428)		3.844 (1.873-7.332)		[85]
HOTTIP	Up		HOXA13		Lymphatic metastasis, TNM stage					[112]
NEAT1	Up				Lymphatic metastasis, distant metastasis					[113,114]
OTUB1-isoform2	Up		N-cadherin, MMP2, MMP9, E-cadherin		Lymphatic metastasis, TNM stage	1,538 (1.044-2.265)	1.615 (1.111-2.348)		1.498 (1.021-2.200)	[86]
PANDAR					Lymphatic metastasis, TNM stage	4.612 (1.59-13.825)	3.113 (1.591-6.093)	3.683 (1.125-12.058)	2.359 (1.153-4.830)	[87]
ZMAT1 transcript variant 2	Down				Lymphatic metastasis, distant metastasis, TNM stage					[115]
JMJD1A	Up		MALAT1, MAPK		Lymphatic metastasis, TNM stage	8.446 (4.480-15.923)		3.988 (1.948-8.167)		[116]
OR3A4	Up		PDLIM2, MACC1, NTN4, GNB2L1	Degradation of the ECM, angiopoiesis, VM	Lymphatic metastasis distant metastasis					[54]
HNF1A-AS1	Down				Lymphatic metastasis					[117]
BANCR	Up				Lymphatic metastasis, distant metastasis	2.457 (1.715-3.521)		1.511 (1.02-2.227)		[118]
DQ786243	Up				Lymphatic metastasis, TNM stage					[119]
XLOC_010235	Up				distant metastasis, TNM stage					[120]
CCAT2	Up				Lymphatic metastasis, distant metastasis, TNM stage	2.631 (1.348-5.672)	2.574 (1.201-5.476)	2.405 (1.194-5.417)	2.315 (1.097-5.283)	[121,122]
Linc-UBC1	Up				Lymphatic metastasis, TNM stage					[123]
HIF1A-AS2	Up				Lymphatic metastasis, TNM stage	2.346 (1.379-3.991)		1.724 (1.002-2.964)		[124]
LET	Down				Lymphatic metastasis, distant metastasis, TNM stage	2.513 (1.414-5.847)		2.275 (1.301-5.176)		[125]
LSINCT5	Up				Lymphatic metastasis, TNM stage		2.501 (1.326-4.719)		1.081 (1.286-3.564)	[126]
AC130710	Up				distant metastasis, TNM stage					[127]
FER1L4	Down				Lymphatic metastasis, distant metastasis, TNM stage					[88]
RuPAR	Down				Lymphatic metastasis, distant metastasis, TNM stage					[128]
H19	Up		miR-675		Lymphatic metastasis, TNM stage	1.170 (1.050-1.304)		1.137 (1.005-1.287)		[129,130]
AC096655.1-002	Down				Lymphatic metastasis, distant metastasis, TNM stage					[131]
SUMO1P3	Up				Lymphatic metastasis					[132]
IGF2	Up				Lymphatic metastasis					[133]
CCAT1	Up				Lymphatic metastasis, TNM stage					[134]

EMT: Epithelial-mesenchymal transition; VM: Vasculogenic mimicry; TNM: Tumor, node, metastasis; ECM: Extracellular matrix.