Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

Table 1 Aberrant expression of lncRNAs and their gene locus, product size, expression status and biological function

lncRNAs	Cancer type	Gene locus	Size	Expression	Correlation with metastasis	Biological function
91H	CRC	11p15.5	119392nt	Up	Positive	Migration and invasiveness[50]
		(H19/IGF2 locus)
AK123657	CRC	NA	2126 nt	Down	Negative	Inhibit cell invasion, and serve as promising biomarkers for prognosis[51]
BX649059			3967 nt	Down	Negative
BX648207			5032 nt	Down	Negative
CCAT1	CRC	8q24.21	2628 nt	Up	Positive	Up-regulated across the colonadenoma-carcinoma sequence and activated by C-myc to promote metastatic process[52,53]
CCAT2	CRC	8q24.21	1752 nt	Up	Positive	Interacts with TCF7L2 which leads to genomic instability, cell invasion and forms a feedback loop with WNT signaling[54]
FER1L4	CRC	20q11.22	6717 nt	Down	Negative	Suppresses oncogenesis via inhibiting miR-106a-5p[55]
HOTAIR	CRC	12q13.13	2370 nt	Up	Positive	Interacts with PRC2 complex and participates in EMT[45,56]; the blood levels of HOTAIR also serves as a negative prognostic factor[46]
LOC285194	CRC	3q13.31	2105 nt	Down	NA	Novel biomarker of cancer metastasis[57]
MALAT1	CRC	11q13.1	8758 nt	Up	Positive	3' end of MALAT-1 (6918 nt-8441 nt) promotes migration and invasion and AKAP-5 is a downstream target protein[58,59]; Mediates Wnt/β-catenin signalling[49]; Upregulated by tumor-associated dendritic cells expressed CCL5 and enhances Snail to promote migration, invasion and EMT[60]
MEG3	CRC	14q32	1595 nt	Down	NA	Potential marker for prognosis[61]
ncRAN	CRC	17q25.1	2538 nt	Up	Positive	Promotes migration and invasion[62]
ncRuPAR	CRC	5q13.3	486 nt	Down	NA	Potential biomarker[63]
NEAT1	CRC	11q13.1	3756 nt	Up	NA	Indicator of tumor differentiation, invasion and metastasis[64]
PVT-1	CRC	8q24	1957 nt	Up	NA	Antiapoptotic activity[65]
TUG1	CRC	22q12.2	7598 nt	Up	Positive	Activates EMT and promotes migration, invasion[66]
91H	ESCC	11p15.5	119.392kb	Down	Negative	Inhibits IGF2 expression and regulates tumor development[67]
AFAP1-AS1	ESCC	(H19/IGF2 locus)	6810 nt	Down	Positive	Hypomethylated and overexpressed in ESCC, promotes migration and invasion in a AFAP1 independent manner[68]
		4p16.1
		(AFAP1 locus)
CCAT2	ESCC	8q24.21	1752 nt	Up	Negative	Potential prognostic biomarker and therapeutic target[69]
H19	ESCC	11p15.5	2362 nt	Up	Positive	H19 CBS6 hypermethylation leads to IGF2 overexpression and cancer progression[70]
		(IGF2 locus)
HNF1A-AS1	ESCC	12q24.31	2455 nt	Up	Positive	Upregulated in primary ESCC , affects assembly of chromatin and the nucleosome process by H19 induction[71]
		(HNF1A locus)
HOTAIR	ESCC	12q13.13	2370 nt	Up	Positive	Medicates migratory capacity[44,72,73]; promotes histone H3K27 methylation and activates Wnt/β-catenin signaling and decreases WIF-1, lead to metastasis[43]
MALAT1	ESCC	11q13.1	> 8 kb	Up	Positive	Target of miR-101 and miR-217 and promotes migration, invasion and metastasis[74]
MALAT1	GBC	11q13.1	8758 nt	Up	Positive	Binds to SFPQ, leading to PTBP2 release from SFPQ/PTBP2 complex[75]; Activates the ERK/MAPK pathway and promotes metastasis[76]
AA174084	GC	13q33.1	601 nt	Up	NA	The expression level in gastric juice is a potential marker for the early diagnosis of GC[48]
AC130710	GC	2p24.3	984 nt	Up	NA	As a target of miR-129-5p and may be a potential biomarker for GC prognosis[77]
AK058003	GC	10q22	1197 nt	Up	NA	Induced by hypoxia and regulates SNCG to promote metastasis[78]
BM742401	GC	18q11.2	1788 nt	Down	Negative	Decreases expression of MMP9 and inhibits metastasis-related phenotypes[79]
FENDRR	GC	3q13.31	3099 nt	Down	Negative	Downregulates FN1 and MMP2/MMP9 to suppress invasion and migration[80]
GAPLINC	GC	18p11.31	924 nt	Up	Positive	Competes to bind with miR-211-3p,which leads to the increased translation of CD44 and promotes proliferation, migration, and angiogenesis[81]
H19	GC	11p15.5	2362 nt	Up	Positive	Target of c-Myc and promotes migration, invasion and metastasis by the direct upregulation of ISM1 and indirect suppression of CALN1 via miR-675[82,83]
		(IGF2 locus)
HOTAIR	GC	12q13.13	2370 nt	Up	Positive	Novel biomarker for prognosis and promotes metastasis via PCBP1 inhibition[61,84-87]; as a ceRNA of miR-331-3p and modulates the derepression of HER2[41]; Upregulates HLA-G via inhibiting miR-152[42]; binds to PRC2 complex and epigenetically represses miR34a, which inhibits HGF/Met/Snail pathway and Snail, leads to EMT and metastasis[55]
HULC	GC	6p24.3	About 1.6 kb	Up	Positive	Promotes EMT[88]
LEIGC	GC	2q14.1	2659 nt	Down	Negative	Inhibits EMT[89]
OR3A4	GC	17p13.3	1202 nt	Up	Positive	Promotes migration, invasion, tubule formation, vasculogenic mimicry, angiogenesis by regulating PDLIM2, MACC1, NTN4, and GNB2L1[90]

CRC: Colorectal cancer; GBC: Gallbladder carcinoma; GC: Gastric cancer; ESCC: Esophageal squamous cell carcinoma; NA: Data not available.