Table I.
lncRNAs in liver fibrosis.
| lncRNAs | Cellular target | Role in liver fibrosis | (Refs.) |
|---|---|---|---|
| Activation of liver fibrosis | |||
| NEAT-1 | miR-122, miR-29b | NEAT-1 promotes liver fibrosis through miR-122/KLF6 and miR-29b/Atg9a pathways | (31-34) |
| HOTAIR | miR-148b, miR-29b | Acts as ceRNA for miR-148b, miR-29b. HOTAIR regulates miR-148b/DNMT1/MEG3/p53 and miR-29b/PTEN pathways in liver fibrosis | (35,36) |
| HOTTIP | miR-148a, miR-150 | Acts as ceRNA for miR-148a and miR-150. Activates TGF-β pathway and induces HSC activation | (37,38) |
| MALAT1 | miR-101b, miR-26b | Promotes liver fibrosis through miR-26b/SIRT1/Smad3 and miR-101b/Ras-Rac1 and CXCL5 pathways | (39-41) |
| HULC | None identified yet | Silencing of HULC improves liver pathology in NAFLD rats through inhibition of MAP kinase pathway | (42) |
| SCARNA10 | PRC2 | Positively regulates TGF-β pathway by inhibiting PRC2 | (43) |
| Lnc-LFAR1 | Smad2/3 | Binds to Smad2/3 in cytoplasm to activate TGF-β and NOTCH pathway. | (44) |
| Linc-SCRG1 | TTP | Binds and inhibits TTP and prevents TTP induced degradation of TNF-α and MMP-2. | (45) |
| SNHG7 | miR-378a-3p | Activates Wnt/β-catenin pathway by negatively regulating miR-378a-3p | (46) |
| PVT1 | miR-152 | Binds as ceRNA to miR-152 which leads to PTCH1 inhibition, resulting in activation of Hedgehog pathway to promote cell migration and liver fibrosis | (47) |
| Lnc RNA-ATB | miR-200a | ATB knockdown reduced β-catenin expression by upregulating miR-200a expression and suppressed LX-2 cells activation | (48) |
| LincRNA-p21 | p21, miR-30, miR-181b, miR-17-5p | Promotes liver fibrosis through multiple pathways involving p21, miR-181b/PTEN miR-17-5p/β-catenin and miR-30 | (49-53) |
| Inhibition of liver fibrosis | |||
| MEG3 | miR-212, SMO | Overexpression of MEG3 inhibited HSC activation, induced hepatocyte apoptosis and reduced α-SMA and type Icollagen | (54-56) |
| GAS5 | miR-23a, miR-222 | Binds as a ceRNA to miR-23a and miR-222 to inhibit PTEN and increase p27 levels respectively | (8,57) |
| Gm5091 | miR-27b, miR-23b, miR-24 | Alleviates alcoholic liver fibrosis by sequestration of miR-23b, miR-27b, miR-24 and down regulation of HSC activation, cell migration, type I collagen expression | (58) |
| HIF1-AS1 | TET3 | HIF1-AS1 inhibits LX-2 cell proliferation and is negatively regulated by TET3 | (59) |
| ANRIL | DNMT3A, AMPK | Overexpression of ANRIL inhibits DNMT3A and AMPK | (60) |
| Dual role in liver fibrosis | |||
| H19 | MeCP2, IGF1R | Overexpression of H19 inhibits liver fibrosis by downregulating pERK1/2 and MeCP2/IGF1R pathways | (64,65) |
| let7, ZEB1 | Promotes cholestatic liver fibrosis by binding to ZEB1 and inhibiting cell migration and activates SIPR2/SphK2/let7/HMGA2 pathway | (66-68) |
The table lists several lncRNAs and their corresponding cellular targets. Most of these targets are miRNAs and in some cases, signaling proteins. Depending on their role in liver fibrosis, they have been categorized in to activators or inhibitors of liver fibrosis. lncRNAs, long non-coding RNAs; miRNAs, microRNAs.