LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology

Abid A. Anwar; Nidhi Jalan-Sakrikar; Robert C. Huebert

doi:10.1055/a-2490-1921

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2025; 45(01): 001-014
DOI: 10.1055/a-2490-1921

Review Article

LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology

Abid A. Anwar

¹Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota

²Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota

,

Nidhi Jalan-Sakrikar

¹Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota

²Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota

³Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic and Foundation, Rochester, Minnesota

,

Robert C. Huebert

¹Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, Minnesota

²Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota

³Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic and Foundation, Rochester, Minnesota

› Author Affiliations

Abstract

The field of ribonucleic acid (RNA) biology has revealed an array of noncoding RNA species, particularly long noncoding RNAs (lncRNAs), which play crucial roles in liver disease pathogenesis. This review explores the diverse functions of lncRNAs in liver pathology, including metabolic-associated steatotic liver disease, hepatocellular carcinoma, alcohol-related liver disease, and cholangiopathies such as primary sclerosing cholangitis and cholangiocarcinoma. We highlight key lncRNAs that regulate lipid metabolism, inflammation, fibrosis, and oncogenesis in the liver, demonstrating their diagnostic and therapeutic potential. Emerging RNA-based therapies, such as mRNA therapy, RNA interference, and antisense oligonucleotides, offer approaches to modulate lncRNA activity and address liver disease at a molecular level. Advances in sequencing technologies and bioinformatics pipelines are simultaneously enabling the identification and functional characterization of novel lncRNAs, driving innovation in personalized medicine. In conclusion, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in liver disease and emphasizes the need for further research into their regulatory mechanisms and clinical applications.

Keywords

lncRNA - liver disease - hepatocyte - cholangiocyte

Full Text

References

References
1 Chang HY, Qi LS. Reversing the central dogma: RNA-guided control of DNA in epigenetics and genome editing. Mol Cell 2023; 83 (03) 442-451
2 Wu J, Xiao J, Zhang Z, Wang X, Hu S, Yu J. Ribogenomics: the science and knowledge of RNA. Genomics Proteomics Bioinformatics 2014; 12 (02) 57-63
3 Mattick J, Amaral P. RNA, the Epicenter of Genetic Information: A New Understanding of Molecular Biology. 1 st ed.. Boca Raton: CRC Press; 2022: 422
4 Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol 2021; 22 (02) 96-118
5 Szcześniak MW, Kubiak MR, Wanowska E, Makałowska I. Comparative genomics in the search for conserved long noncoding RNAs. Essays Biochem 2021; 65 (04) 741-749
6 Long Y, Wang X, Youmans DT, Cech TR. How do lncRNAs regulate transcription?. Sci Adv 2017; 3 (09) eaao2110
7 Ruan X, Li P, Ma Y. et al. Identification of human long noncoding RNAs associated with nonalcoholic fatty liver disease and metabolic homeostasis. J Clin Invest 2021; 131 (01) e136336
8 Meng X, Long M, Yue N. et al. LncRNA MEG3 restrains hepatic lipogenesis via the FOXO1 signaling pathway in HepG2 cells. Cell Biochem Biophys 2024; 82 (02) 1253-1259
9 Yang S, Zhang Y, Zhang Y. et al. LncRNA Gm28382 promotes lipogenesis by interacting with miR-326-3p to regulate ChREBP signaling pathway in NAFLD. Int Immunopharmacol 2024; 127: 111444
10 Yuan X, Liu Y, Yang X. et al. Long noncoding RNA lnc_217 regulates hepatic lipid metabolism by modulating lipogenesis and fatty acid oxidation. J Biomed Res 2023; 37 (06) 448-459
11 Wang P, Wang X, He D, Zhuang C. LncRNA AK142643 promotes hepatic lipid accumulation by upregulating CD36 via interacting with IGF2BP2. Gene 2023; 887: 147747
12 Guo B, Yan S, Zhai L, Cheng Y. LncRNA HOTAIR accelerates free fatty acid-induced inflammatory response in HepG2 cells by recruiting SRSF1 to stabilize MLXIPL mRNA. Cytotechnology 2024; 76 (02) 259-269
13 Li SP, Xu HX, Yu Y. et al. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway. Oncotarget 2016; 7 (27) 42431-42446
14 Shen X, Guo H, Xu J, Wang J. Inhibition of lncRNA HULC improves hepatic fibrosis and hepatocyte apoptosis by inhibiting the MAPK signaling pathway in rats with nonalcoholic fatty liver disease. J Cell Physiol 2019; 234 (10) 18169-18179
15 Lu J, Guo J, Liu J, Mao X, Xu K. Long non-coding RNA MALAT1: a key player in liver diseases. Front Med (Lausanne) 2022; 8: 734643
16 Cheng X, Shihabudeen Haider Ali MS, Moran M. et al. Long non-coding RNA Meg3 deficiency impairs glucose homeostasis and insulin signaling by inducing cellular senescence of hepatic endothelium in obesity. Redox Biol 2021; 40: 101863
17 Han MH, Lee JH, Kim G. et al. Expression of the long noncoding RNA GAS5 correlates with liver fibrosis in patients with nonalcoholic fatty liver disease. Genes (Basel) 2020; 11 (05) 545
18 Chen T, Meng Y, Zhou Z. et al. GAS5 protects against nonalcoholic fatty liver disease via miR-28a-5p/MARCH7/NLRP3 axis-mediated pyroptosis. Cell Death Differ 2023; 30 (07) 1829-1848
19 Cui J, Wang Y, Xue H. Long non-coding RNA GAS5 contributes to the progression of nonalcoholic fatty liver disease by targeting the microRNA-29a-3p/NOTCH2 axis. Bioengineered 2022; 13 (04) 8370-8381
20 Sun C, Zhou C, Daneshvar K. et al. Conserved long noncoding RNA TILAM promotes liver fibrosis through interaction with PML in HSCs. Hepatology 2024;
21 Liu S, Huttad L, He G. et al. Long noncoding RNA HULC regulates the NF-κB pathway and represents a promising prognostic biomarker in liver cancer. Cancer Med 2023; 12 (04) 5124-5136
22 Lumkul L, Jantaree P, Jaisamak K. et al. Combinatorial gene expression profiling of serum HULC, HOTAIR, and UCA1 lncRNAs to differentiate hepatocellular carcinoma from liver diseases: a systematic review and meta-analysis. Int J Mol Sci 2024; 25 (02) 1258
23 Yao Y, Duan C, Chen Y. et al. Long non-coding RNA detection based on multi-probe-induced rolling circle amplification for hepatocellular carcinoma early diagnosis. Anal Chem 2023; 95 (02) 1549-1555
24 Berhane T, Holm A, Karstensen KT. et al. Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin. Sci Rep 2022; 12 (01) 19502
25 Feng T, Yao Y, Luo L. et al. ST8SIA6-AS1 contributes to hepatocellular carcinoma progression by targeting miR-142-3p/HMGA1 axis. Sci Rep 2023; 13 (01) 650
26 Chen R, Zhao M, An Y, Liu D, Tang Q. GBAP1 functions as a tumor promotor in hepatocellular carcinoma via the PI3K/AKT pathway. BMC Cancer 2023; 23 (01) 628
27 Peng YL, Dong YF, Guo LL, Li MY, Liao H, Li RS. Identification and validation of a m7G-related lncRNA signature for predicting the prognosis and therapy response in hepatocellular carcinoma. PLoS One 2023; 18 (08) e0289552
28 Wang RY, Yang JL, Xu N. et al. Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma. World J Gastroenterol 2024; 30 (08) 919-942
29 Fei M, Li X, Liang S. et al. LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity. Cancer Lett 2024; 584: 216620
30 Leti F, Legendre C, Still CD. et al. Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells. Transl Res 2017; 190: 25-39.e21
31 Toraih EA, Ellawindy A, Fala SY. et al. Oncogenic long noncoding RNA MALAT1 and HCV-related hepatocellular carcinoma. Biomed Pharmacother 2018; 102: 653-669
32 Wang B, Li X, Hu W, Zhou Y, Din Y. Silencing of lncRNA SNHG20 delays the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma via regulating liver Kupffer cells polarization. IUBMB Life 2019; 71 (12) 1952-1961
33 Wang H, Wang Y, Lai S. et al. LINC01468 drives NAFLD-HCC progression through CUL4A-linked degradation of SHIP2. Cell Death Discov 2022; 8 (01) 449
34 Yang Z, Ross RA, Zhao S, Tu W, Liangpunsakul S, Wang L. LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis. Hepatol Commun 2017; 1 (06) 513-523
35 Yan Y, Ren L, Liu Y, Liu L. Long non-coding RNA CRNDE as potential biomarkers facilitate inflammation and apoptosis in alcoholic liver disease. Aging (Albany NY) 2021; 13 (19) 23233-23244
36 Jin J, Nguyen LTG, Wassef A. et al. Identification and functional characterization of alternative transcripts of LncRNA HNF1A-AS1 and their impacts on cell growth, differentiation, liver diseases, and in response to drug induction. Noncoding RNA 2024; 10 (02) 28
37 Zhong B, Dong J, Zhang R. et al. Altered regulation of LncRNA analysis of human alcoholic hepatitis with Mallory-Denk Bodies (MDBs) is revealed by RNA sequencing. Exp Mol Pathol 2020; 117: 104559
38 Sun SY, Lee DH, Liu HC, Yang Y, Han YH, Kwon T. Identifying competing endogenous RNA regulatory networks and hub genes in alcoholic liver disease for early diagnosis and potential therapeutic target insights. Aging (Albany NY) 2024; 16 (10) 9147-9167
39 Zhao X, Fan H, Chen X. et al. Hepatitis B virus DNA polymerase restrains viral replication through the CREB1/HOXA distal transcript antisense RNA homeobox A13 axis. Hepatology 2021; 73 (02) 503-519
40 Guo Y, Li C, Zhang R. et al. Epigenetically-regulated serum GAS5 as a potential biomarker for patients with chronic hepatitis B virus infection. Cancer Biomark 2021; 32 (02) 137-146
41 Sun CX, Han LY, Wang K, Gao S. Serum exosomal long noncoding RNA growth arrest-specific 5 predicts 3-month mortality in acute-on-chronic hepatitis B liver failure. J Inflamm Res 2023; 16: 4603-4616
42 Qin Y, Ren J, Yu H. et al. HOXA-AS2 epigenetically inhibits HBV transcription by recruiting the MTA1-HDAC1/2 deacetylase complex to cccDNA minichromosome. Adv Sci (Weinh) 2024; 11 (24) e2306810
43 Yao Y, Shu F, Wang F. et al. Long noncoding RNA LINC01189 is associated with HCV-hepatocellular carcinoma and regulates cancer cell proliferation and chemoresistance through hsa-miR-155-5p. Ann Hepatol 2021; 22: 100269
44 Khatun M, Sur S, Steele R, Ray R, Ray RB. Inhibition of long noncoding RNA Linc-Pint by hepatitis C virus in infected hepatocytes enhances lipogenesis. Hepatology 2021; 74 (01) 41-54
45 Kitabayashi J, Shirasaki T, Shimakami T. et al; Hokuriku Liver Study Group. Upregulation of the long noncoding RNA HULC by hepatitis C virus and its regulation of viral replication. J Infect Dis 2022; 226 (03) 407-419
46 Banales JM, Huebert RC, Karlsen T, Strazzabosco M, LaRusso NF, Gores GJ. Cholangiocyte pathobiology. Nat Rev Gastroenterol Hepatol 2019; 16 (05) 269-281
47 Lazaridis KN, LaRusso NF. Primary sclerosing cholangitis. N Engl J Med 2016; 375 (25) 2501-2502
48 Li M, Zhou Y, Zhu H, Xu LM, Ping J. Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation. J Integr Med 2024; 22 (02) 188-198
49 Popov Y, Patsenker E, Fickert P, Trauner M, Schuppan D. Mdr2 (Abcb4)-/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes. J Hepatol 2005; 43 (06) 1045-1054
50 Li X, Liu R, Huang Z. et al. Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans. Hepatology 2018; 68 (02) 599-615
51 Li X, Liu R, Yang J. et al. The role of long noncoding RNA H19 in gender disparity of cholestatic liver injury in multidrug resistance 2 gene knockout mice. Hepatology 2017; 66 (03) 869-884
52 Li X, Liu R, Wang Y. et al. Cholangiocyte-derived exosomal lncRNA H19 promotes macrophage activation and hepatic inflammation under cholestatic conditions. Cells 2020; 9 (01) 190
53 Li XJ, Zhou F, Li YJ. et al. LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles. Acta Pharmacol Sin 2023; 44 (12) 2479-2491
54 Liu R, Li X, Zhu W. et al. Cholangiocyte-derived exosomal long noncoding RNA H19 promotes hepatic stellate cell activation and cholestatic liver fibrosis. Hepatology 2019; 70 (04) 1317-1335
55 Navarro-Corcuera A, Sehrawat TS, Jalan-Sakrikar N. et al. Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex. J Hepatol 2022; 76 (04) 921-933
56 She C, Yang Y, Zang B. et al. Effect of LncRNA XIST on immune cells of primary biliary cholangitis. Front Immunol 2022; 13: 816433
57 Hagenbeck C, Hamza A, Kehl S. et al. Management of intrahepatic cholestasis of pregnancy: recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd 2021; 81 (08) 922-939
58 Hu J, Liu L, Gong Y. et al. Linc02527 promoted autophagy in Intrahepatic cholestasis of pregnancy. Cell Death Dis 2018; 9 (10) 979
59 Zou S, Zhao S, Wang J. et al. Diagnostic and prognostic value of long noncoding RNAs as potential novel biomarkers in intrahepatic cholestasis of pregnancy. BioMed Res Int 2021; 2021: 8858326
60 Tam PKH, Wells RG, Tang CSM. et al. Biliary atresia. Nat Rev Dis Primers 2024; 10 (01) 47
61 Nuerzhati Y, Dong R, Song Z, Zheng S. Role of the long non–coding RNA–Annexin A2 pseudogene 3/Annexin A2 signaling pathway in biliary atresia–associated hepatic injury. Int J Mol Med 2019; 43 (02) 739-748
62 Ye Y, Wu W, Zheng J, Zhang L, Wang B. Role of long non-coding RNA-adducin 3 antisense RNA1 in liver fibrosis of biliary atresia. Bioengineered 2022; 13 (03) 6222-6230
63 Chansitthichok S, Chamnan P, Sarkhampee P, Lertsawatvicha N, Voravisutthikul P, Wattanarath P. Survival of patients with cholangiocarcinoma receiving surgical treatment in an O. viverrini endemic area in Thailand: a retrospective cohort study. Asian Pac J Cancer Prev 2020; 21 (04) 903-909
64 Shobeiri P, Arabzadeh Bahri R, Khadembashiri MM. et al. Role of long non-coding RNAs in cholangiocarcinoma: a systematic review and meta-analysis. Cancer Rep (Hoboken) 2024; 7 (03) e2029
65 Smirnova OV, Ostroukhova TY, Bogorad RL. JAK-STAT pathway in carcinogenesis: is it relevant to cholangiocarcinoma progression?. World J Gastroenterol 2007; 13 (48) 6478-6491
66 Yu S, Gao X, Liu S. et al. LOXL1-AS1 inhibits JAK2 ubiquitination and promotes cholangiocarcinoma progression through JAK2/STAT3 signaling. Cancer Gene Ther 2024; 31 (04) 552-561
67 Papoutsoglou P, Pineau R, Leroux R. et al. TGFβ-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma. EMBO Rep 2024; 25 (03) 1022-1054
68 Ni Q, Zhang H, Shi X, Li X. Exosomal lncRNA HCG18 contributes to cholangiocarcinoma growth and metastasis through mediating miR-424-5p/SOX9 axis through PI3K/AKT pathway. Cancer Gene Ther 2023; 30 (04) 582-595
69 Lei S, Cao W, Zeng Z. et al. JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis. Cell Death Dis 2022; 13 (11) 967
70 Sun D, Li F, Liu L. et al. PSMA3-AS1 induced by transcription factor PAX5 promotes cholangiocarcinoma proliferation, migration and invasion by sponging miR-376a-3p to up-regulate LAMC1. Aging (Albany NY) 2022; 14 (01) 509-525
71 Li F, Chen Q, Xue H, Zhang L, Wang K, Shen F. LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis. Cell Death Dis 2020; 11 (10) 894
72 Zhu H, Zhai B, He C. et al. LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis. Cell Death Dis 2020; 11 (08) 637
73 Iyer MK, Niknafs YS, Malik R. et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 2015; 47 (03) 199-208
74 Sun M, Kraus WL. From discovery to function: the expanding roles of long noncoding RNAs in physiology and disease. Endocr Rev 2015; 36 (01) 25-64
75 Wang J, Fang Y, Luo Z, Wang J, Zhao Y. Emerging mRNA technology for liver disease therapy. ACS Nano 2024; 18 (27) 17378-17406
76 Guo Z, Zeng C, Shen Y. et al. Helper lipid-enhanced mRNA delivery for treating metabolic dysfunction-associated fatty liver disease. Nano Lett 2024; 24 (22) 6743-6752
77 Rizvi F, Lee YR, Diaz-Aragon R. et al. VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis. bioRxiv 2023;
78 Diwan R, Gaytan SL, Bhatt HN, Pena-Zacarias J, Nurunnabi M. Liver fibrosis pathologies and potentials of RNA based therapeutics modalities. Drug Deliv Transl Res 2024; 14 (10) 2743-2770
79 Wei G, Cao J, Huang P. et al. Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4^-/- mouse model of PFIC3. J Hepatol 2021; 74 (06) 1416-1428
80 Gurung S, Timmermand OV, Perocheau D. et al. mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria. Sci Transl Med 2024; 16 (729) eadh1334
81 Connolly B, Isaacs C, Cheng L, Asrani KH, Subramanian RR. SERPINA1 mRNA as a treatment for alpha-1 antitrypsin deficiency. J Nucleic Acids 2018; 2018: 8247935
82 Rizvi F, Everton E, Smith AR. et al. Murine liver repair via transient activation of regenerative pathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified mRNA. Nat Commun 2021; 12 (01) 613
83 Gonzalez-Rodriguez A, Valverde AM. RNA interference as a therapeutic strategy for the treatment of liver diseases. Curr Pharm Des 2015; 21 (31) 4574-4586
84 Kang C. Lumasiran: a review in primary hyperoxaluria type 1. Drugs 2024; 84 (02) 219-226
85 Lamb YN. Inclisiran: first approval. Drugs 2021; 81 (03) 389-395
86 Goldfarb DS, Lieske JC, Groothoff J. et al. Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4). Urolithiasis 2023; 51 (01) 80
87 Titze-de-Almeida SS, Brandão PRP, Faber I, Titze-de-Almeida R. Leading RNA interference therapeutics part 1: silencing hereditary transthyretin amyloidosis, with a focus on patisiran. Mol Diagn Ther 2020; 24 (01) 49-59
88 Adams D, Gonzalez-Duarte A, O'Riordan WD. et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018; 379 (01) 11-21
89 Nie T, Heo YA, Shirley M. Vutrisiran: a review in polyneuropathy of hereditary transthyretin-mediated amyloidosis. Drugs 2023; 83 (15) 1425-1432
90 Syed YY. Givosiran: a review in acute hepatic porphyria. Drugs 2021; 81 (07) 841-848
91 Zhang MM, Bahal R, Rasmussen TP, Manautou JE, Zhong XB. The growth of siRNA-based therapeutics: Updated clinical studies. Biochem Pharmacol 2021; 189: 114432
92 Strnad P, Mandorfer M, Choudhury G. et al. Fazirsiran for liver disease associated with alpha₁-antitrypsin deficiency. N Engl J Med 2022; 387 (06) 514-524
93 Wooddell CI, Blomenkamp K, Peterson RM. et al. Development of an RNAi therapeutic for alpha-1-antitrypsin liver disease. JCI Insight 2020; 5 (12) e135348
94 Clark VC, Strange C, Strnad P. et al. Fazirsiran for adults with alpha-1 antitrypsin deficiency liver disease: a phase 2 placebo controlled trial (SEQUOIA). Gastroenterology 2024; 167 (05) 1008-1018.e5
95 Dehghan H, Ghasempour A, Sabeti Akbar-Abad M. et al. An update on the therapeutic role of RNAi in NAFLD/NASH. Prog Mol Biol Transl Sci 2024; 204: 45-67
96 Mak LY, Gane E, Schwabe C. et al. A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis. J Hepatol 2023; 78 (04) 684-692
97 Luukkonen PK, Sakuma I, Gaspar RC. et al. Inhibition of HSD17B13 protects against liver fibrosis by inhibition of pyrimidine catabolism in nonalcoholic steatohepatitis. Proc Natl Acad Sci U S A 2023; 120 (04) e2217543120
98 Zhou J, Xu S, Zhu Y. et al. Inhibition of neuropilin-1 improves non-alcoholic fatty liver disease in high-fat-diet induced obese mouse. Minerva Endocrinol (Torino) 2023; 48 (02) 194-205
99 Craig K, Abrams M, Amiji M. Cholesterol-conjugated siRNA silencing Tnf for the treatment of liver macrophage-mediated acute inflammation in nonalcoholic fatty liver disease. Nucleic Acid Ther 2023; 33 (01) 35-44
100 Li T, Huang X, Yue Z, Meng L, Hu Y. Knockdown of long non-coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non-alcoholic fatty liver disease. Cell Biochem Funct 2020; 38 (07) 839-846
101 Jin X, Gao J, Zheng R. et al. Antagonizing circRNA_002581-miR-122-CPEB1 axis alleviates NASH through restoring PTEN-AMPK-mTOR pathway regulated autophagy. Cell Death Dis 2020; 11 (02) 123
102 Ahn J, Lee H, Jung CH. et al. 6-Gingerol ameliorates hepatic steatosis via HNF4α/miR-467b-3p/GPAT1 cascade. Cell Mol Gastroenterol Hepatol 2021; 12 (04) 1201-1213
103 Tripathi SK, Pal A, Ghosh S. et al. LncRNA NEAT1 regulates HCV-induced hepatocellular carcinoma by modulating the miR-9-BGH3 axis. J Gen Virol 2022; 103 (12)
104 Fiflis DN, Rey NA, Venugopal-Lavanya H. et al. Repurposing CRISPR-Cas13 systems for robust mRNA trans-splicing. Nat Commun 2024; 15 (01) 2325
105 Yoon PH, Zhang Z, Loi KJ. et al. Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases. Science 2024; 385 (6708) 538-543
106 Chen J, Wang R, Xiong F. et al. Hammerhead-type FXR agonists induce an enhancer RNA Fincor that ameliorates nonalcoholic steatohepatitis in mice. eLife 2024; 13: RP91438
107 Hernandez ED, Zheng L, Kim Y. et al. Tropifexor-mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents. Hepatol Commun 2019; 3 (08) 1085-1097
108 Tully DC, Rucker PV, Chianelli D. et al. Discovery of tropifexor (LJN452), a highly potent non-bile acid FXR agonist for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH). J Med Chem 2017; 60 (24) 9960-9973
109 Sanyal AJ, Lopez P, Lawitz EJ. et al. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial. Nat Med 2023; 29 (02) 392-400
110 Chan YT, Wu J, Lu Y. et al. Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC. Mol Cancer 2024; 23 (01) 74
111 Sun Z, Xue S, Zhang M. et al. Aberrant NSUN2-mediated m⁵C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma. Oncogene 2020; 39 (45) 6906-6919
112 Ali HS, Boshra MS, El Meteini MS, Shafei AE, Matboli M. lncRNA- RP11-156p1.3, novel diagnostic and therapeutic targeting via CRISPR/Cas9 editing in hepatocellular carcinoma. Genomics 2020; 112 (05) 3306-3314
113 Li D, Mastaglia FL, Fletcher S, Wilton SD. Precision medicine through antisense oligonucleotide-mediated exon skipping. Trends Pharmacol Sci 2018; 39 (11) 982-994
114 Dave P, Anand P, Kothawala A. et al. RNA interference therapeutics for hereditary amyloidosis: a narrative review of clinical trial outcomes and future directions. Cureus 2024; 16 (06) e62981
115 Li S, Xiong F, Zhang S. et al. Oligonucleotide therapies for nonalcoholic steatohepatitis. Mol Ther Nucleic Acids 2024; 35 (02) 102184
116 Ma Y, Cai H, Smith J. et al. Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model. J Lipid Res 2024; 65 (03) 100514
117 Wu M, Lo TH, Li L. et al. Amelioration of non-alcoholic fatty liver disease by targeting adhesion G protein-coupled receptor F1 (Adgrf1). eLife 2023; 12: e85131
118 Caputo M, Kurhe Y, Kumari S. et al Silencing of STE20-type kinase MST3 in mice with antisense oligonucleotide treatment ameliorates diet-induced nonalcoholic fatty liver disease. FASEB J 2021; May; 35 (05) e21567
119 Hsieh J, Molusky MM, McCabe KM. et al. TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion. J Hepatol 2022; 76 (02) 383-393
120 Worley BL, Auen T, Arnold AC, Monia BP, Hempel N, Czyzyk TA. Antisense oligonucleotide-mediated knockdown of Mpzl3 attenuates the negative metabolic effects of diet-induced obesity in mice. Physiol Rep 2021; 9 (09) e14853
121 Win S, Min RWM, Zhang J. et al. Hepatic mitochondrial SAB deletion or knockdown alleviates diet-induced metabolic syndrome, steatohepatitis, and hepatic fibrosis. Hepatology 2021; 74 (06) 3127-3145
122 Yong J, Parekh VS, Reilly SM. et al. Chop/Ddit3 depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice. Sci Transl Med 2021; 13 (604) eaba9796
123 Yu J, Zhu C, Wang X. et al. Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis. Sci Transl Med 2021; 13 (599) eabe1692
124 Kim TH, Lee SW. Generation of hepatitis C virus-resistant liver cells by genome editing-mediated stable expression of RNA aptamer. Mol Ther Methods Clin Dev 2023; 31: 101151
125 Lee CH, Lee SH, Kim JH, Noh YH, Noh GJ, Lee SW. Pharmacokinetics of a cholesterol-conjugated aptamer against the hepatitis C Virus (HCV) NS5B protein. Mol Ther Nucleic Acids 2015; 4 (10) e254
126 Liu Z, Sun X, Xiao S. et al. Characterization of aptamer-mediated gene delivery system for liver cancer therapy. Oncotarget 2017; 9 (06) 6830-6840
127 Xiao S, Liu Z, Deng R. et al. Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo. J Control Release 2017; 258: 130-145
128 Lee YJ, Lee SW. Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein. Biochem Biophys Res Commun 2012; 417 (01) 521-527
129 Lee YJ, Han SR, Kim NY, Lee SH, Jeong JS, Lee SW. An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice. Gastroenterology 2012; 143 (01) 155-65.e8
130 Bhattacharya SD, Mi Z, Kim VM, Guo H, Talbot LJ, Kuo PC. Osteopontin regulates epithelial mesenchymal transition-associated growth of hepatocellular cancer in a mouse xenograft model. Ann Surg 2012; 255 (02) 319-325
131 Sriram K, Luo Y, Malhi NK, Chen AT, Chen ZB. Methods to study RNA-chromatin interactions. Methods Mol Biol 2023; 2666: 279-297
132 Sun Z, Nair A, Chen X, Prodduturi N, Wang J, Kocher JP. UClncR: ultrafast and comprehensive long non-coding RNA detection from RNA-seq. Sci Rep 2017; 7 (01) 14196
133 Chu C, Quinn J, Chang HY. Chromatin isolation by RNA purification (ChIRP). J Vis Exp 2012; (61) 3912
134 Quinn JJ, Ilik IA, Qu K. et al. Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Nat Biotechnol 2014; 32 (09) 933-940
135 Wong LS, Wei L, Wang G. et al. In vivo genome-wide CRISPR activation screening identifies functionally important long noncoding RNAs in hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol 2022; 14 (05) 1053-1076
136 Mondal T, Subhash S, Kanduri C. Chromatin RNA immunoprecipitation (ChRIP). Methods Mol Biol 2018; 1689: 65-76
137 Gagliardi M, Matarazzo MR. RIP: RNA immunoprecipitation. Methods Mol Biol 2016; 1480: 73-86
138 Subramanian P, Gargani S, Palladini A. et al. The RNA binding protein human antigen R is a gatekeeper of liver homeostasis. Hepatology 2022; 75 (04) 881-897
139 Chen Y, Huang H, Xu C, Yu C, Li Y. Long non-coding RNA profiling in a non-alcoholic fatty liver disease rodent model: new insight into pathogenesis. Int J Mol Sci 2017; 18 (01) 21
140 Jazurek M, Ciesiolka A, Starega-Roslan J, Bilinska K, Krzyzosiak WJ. Identifying proteins that bind to specific RNAs - focus on simple repeat expansion diseases. Nucleic Acids Res 2016; 44 (19) 9050-9070
141 Xing Z, Lin C, Yang L. LncRNA pulldown combined with mass spectrometry to identify the novel LncRNA-associated proteins. Methods Mol Biol 2016; 1402: 1-9