Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy

Abstract

Long non-coding RNAs (lncRNAs) are important biological mediators that regulate numerous cellular processes. New experimental evidence suggests that lncRNAs play essential roles in liver development, normal liver physiology, fibrosis, and malignancy, including hepatocellular carcinoma and cholangiocarcinoma. In this review, we summarise our current understanding of the function of lncRNAs in the liver in both health and disease, as well as discuss approaches that could be used to target these non-coding transcripts for therapeutic purposes.

Keywords: ABCA1, ATP-binding cassette transporter A1; ACTA2/ɑ-SMA, α-smooth muscle actin; APO, apolipoprotein; ASO, antisense oligonucleotides; BDL, bile duct ligation; CCA, cholangiocarcinoma; CCl4, carbon tetrachloride; COL1A1, collagen type I α 1; CYP, cytochrome P450; Cholangiocarcinoma; DANCR, differentiation antagonising non-protein coding RNA; DE, definitive endoderm; DEANR1, definitive endoderm-associated lncRNA1; DIGIT, divergent to goosecoid, induced by TGF-β family signalling; DILC, downregulated in liver cancer stem cells; EST, expression sequence tag; EpCAM, epithelial cell adhesion molecule; FBP1, fructose-bisphosphatase 1; FENDRR, foetal-lethal non-coding developmental regulatory RNA; FXR, farnesoid X receptor; GAS5, growth arrest-specific transcript 5; H3K18ac, histone 3 lysine 18 acetylation; H3K36me3, histone 3 lysine 36 trimethylation; H3K4me3, histone 3 lysine 4 trimethylation; HCC, hepatocellular carcinoma; HEIH, high expression In HCC; HNRNPA1, heterogenous nuclear protein ribonucleoprotein A1; HOTAIR, HOX transcript antisense RNA; HOTTIP, HOXA transcript at the distal tip; HSC, hepatic stellate cells; HULC, highly upregulated in liver cancer; Hepatocellular carcinoma; HuR, human antigen R; LCSC, liver cancer stem cell; LSD1, lysine-specific demethylase 1; LXR, liver X receptors; LeXis, liver-expressed LXR-induced sequence; Liver cancer; Liver fibrosis; Liver metabolism; Liver-specific lncRNAs; LncLSTR, lncRNA liver-specific triglyceride regulator; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MEG3, maternally expressed gene 3; NAT, natural antisense transcript; NEAT1, nuclear enriched abundant transcript 1; ORF, open reading frame; PKM2, pyruvate kinase muscle isozyme M2; PPAR-α, peroxisome proliferator-activated receptor-α; PRC, polycomb repressive complex; RACE, rapid amplification of cDNA ends; RNA Pol, RNA polymerase; S6K1, S6 kinase 1; SHP, small heterodimer partner; SREBPs, steroid response binding proteins; SREs, sterol response elements; TGF-β, transforming growth factor-β; TTR, transthyretin; XIST, X-inactive specific transcript; ZEB1, zinc finger E-box-binding homeobox 1; ceRNA, competing endogenous RNA; eRNA, enhancer RNAs; lincRNA, long intervening non-coding RNA; lncRNA; lncRNA, long non-coding RNA; mTOR, mammalian target of rapamycin; siRNA, small interfering RNA.