Long noncoding RNAs in hepatitis B virus replication and oncogenesis

Table 1 Long noncoding RNAs up-regulated in hepatitis B virus-related hepatocellular carcinoma

LncRNA name	Regulatory mechanism	Biological function
HULC[43]	Sequesters microRNAs and decreases p18 expression	Promotes proliferation of hepatoma cells and tumor angiogenesis in vitro and in vivo
HOTAIR[45,47]	Suppresses miRNA-218 expression and inactivation of P14 and P16 signaling	Promotes migration and invasion of HCC cells
HEIH[48]	Binds to EZH2 and represses EZH2 targets	Promotes cell proliferation and tumor growth, modulates cell cycle
HBx-LINE1[16,49]	Sequesters miR-122 and activates Wnt signaling pathway	Promotes cell motility through EMT
UCA1[53,54]	Through the HBx/UCA1/EZH2/p27 axis in nucleus; sequesters miR-216b and miR-203 in cytoplasm	Promotes growth, metastasis, and EMT of HCC cell lines
DBH-AS1[56]	Activates the ERK/p38/JNK MAPK signaling pathway	Inhibits serum starvation-induced apoptosis of HCC cells, promotes tumor growth, proliferation, and cell-cycle progression of HCC cells
HOTTIP[57]	Upregulates the expression of HOXA genes (e.g., HOXA 10, 11, and 13)	Inhibits proliferation and migration of HCC cells in vitro and reduces tumorigenesis and pulmonary metastasis in vivo
ANRIL[59,60]	Represses the KLF2 transcription through binding to PRC2; serves as a molecular sponge for miR-122-5p	Inhibits apoptosis of HCC cells in vitro and promotes proliferation, invasion, and migration of HCC cells in vitro
LINC00152[61]	Inhibits the expression of E-cadherin; activates the mTOR pathway	Promotes the proliferation and EMT of HCC cell lines and tumorigenesis
MALAT1[63,66]	Upregulates LTBP3 transcription	Promotes migration and invasion of HCC cells in vitro and tumor growth in vivo
Ftx[22]	Production of miR-545/374a	Promotes tumorigenesis and tumor progression
MVIH[68]	Activates angiogenesis through reducing the secretion of PGK1	Promotes tumor growth and metastasis
Unigene56159[69]	Sequesters miR-140-5p	Promotes EMT, migration, and invasion of hepatoma cells
LINC01232[70]	Downregulation of miR-708-5p	Promotes tumor progression in vitro
SAMD12-AS1[71]	Inhibition of p53	Promotes cell proliferation and inhibits apoptosis
lnc-HUR1[72]	Inhibition of p53	Promotes cell proliferation and tumorigenesis
n335586[73]	n335586/miR-924/CKMT1A axis	Contributes to cell migration and invasion
XIST[74]	XIST/miR-192/TRIM25 axis	Enhances the proliferation and migration of HCC cells
SNHG5[81]	SNHG5/miR-26a-5p/GSK3β signaling pathway	Promotes HCC progression
WEE2-AS1[76]	HBx/WEE2-AS1/FERMT3 pathway	Promotes HCC proliferation and invasion
MAFG-AS1[77]	HBx/ MAFG-AS1/MAFG	Promotes HCC proliferation and migration
lncRNA-ATB[78]	Induces autophagy	Promotes cell invasion and migration
TRERNA1[79]	TRERNA1/miR-22-3p/NRAS axis	Promotes cell proliferation in HCC
lncRNA IHS[80]	Regulates the ERK- and AKT/GSK-3β signaling pathways	Promotes tumor proliferation and metastasis in HCC
SNHG20[81]	Negatively regulated PTEN protein level	Facilitates the proliferation of HCC cells
AX800134[82]	Not known	Antiapoptosis

LncRNAs: Long noncoding RNAs; HCC: Hepatocellular carcinoma; EMT: Epithelial-to-mesenchymal transition; HULC: Highly upregulated in liver cancer; HBV: Hepatitis B virus; HBx: HBV X protein; LINE: Long interspersed nuclear elements; HOTTIP: HOXA transcript at the distal tip; HOTAIR: HOX transcript antisense RNA; GAS5: Growth arrest specific transcript 5; MEG3: Maternally expressed gene-3; MALAT1: Metastasis associated in lung adenocarcinoma transcript 1; PGK1: Phosphoglycerate kinase 1.

Table 2 Long noncoding RNAs downregulated in hepatitis B virus-related hepatocellular carcinoma

LncRNA name	Regulatory mechanism	Biological function
Dreh[84]	Inhibits the vimentin expression and alters its structure	Inhibits proliferation of HCC cells in vitro and tumor growth in vivo
LET[85]	LET/NF90/HIF1-α axis	Inhibits HCC invasion
uc.306[87]	May participate in the Wnt pathway	Not known
UPAT[88]	Promotes ZEB1 degradation	Suppresses cellular migration, invasion, and EMT processes
SEMA6A-AS1[89]	Not known	Not known
BANCR[90]	Not known	Not known
miR143HG[91]	Suppresses the MAPK and Wnt signaling pathways	Inhibits tumor multiplication and metastasis
LncRNA-6195[92]	Represses the enzymatic activity of ENO1	Represses the growth of HCC
LINC01352[93]	LINC01352/miR-135b/APC axis	Facilitates HCC progression
F11-AS1[94]	lncRNA F11-AS1/miR-211-5p/NR1l3 axis	Inhibits HCC growth and metastasis

LncRNAs: Long noncoding RNAs; HCC: Hepatocellular carcinoma; EMT: Epithelial-to-mesenchymal transition; HIF-1α: Hypoxia induced factor 1-α.