Abstract
MicroRNAs (MiRNAs) are endogenous non-coding small RNA molecules that regulate gene expression in plants, animals and some viruses. Both normal and pathological liver processes are regulated by miRNAs. Recent research indicated that miRNAs have been implicated in liver diseases caused by viral hepatitis (Hepatitis B and Hepatitis C), metabolic problems, alcohol and drug abuse. Because altered miRNA expression is linked to liver metabolic dysregulation, liver damage, liver fibrosis, and tumour growth, miRNAs are promising therapeutic targets for the detection and treatment of liver diseases. In this review, we summarise the current knowledge about the role of microRNAs in acute and chronic liver diseases, including hepatocellular carcinoma. We cover the miRNA-based therapy for liver disorders as well as the use of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases. The investigation of miRNAs in liver diseases will provide a better understanding of the pathogeneses, identification of biomarkers and therapeutic targets for liver diseases in the future.
Keywords: NAFLD, ALD, Viral hepatitis, Liver fibrosis, HCC, MiRNAs.
[http://dx.doi.org/10.1055/s-0034-1397345]
[http://dx.doi.org/10.1093/bib/bbx130] [PMID: 29045685]
[http://dx.doi.org/10.1038/nrm3838] [PMID: 25027649]
[http://dx.doi.org/10.1038/ncb0309-228] [PMID: 19255566]
[http://dx.doi.org/10.1111/j.1365-2141.2008.07077.x] [PMID: 18318758]
[http://dx.doi.org/10.1038/nrclinonc.2011.76] [PMID: 21647195]
[http://dx.doi.org/10.1111/febs.12806] [PMID: 24702768]
[http://dx.doi.org/10.3892/mmr.2021.12137] [PMID: 33955511]
[http://dx.doi.org/10.1002/hep.22737] [PMID: 19072831]
[http://dx.doi.org/10.1007/s11095-011-0473-y] [PMID: 21562928]
[http://dx.doi.org/10.1016/j.cmet.2012.04.004] [PMID: 22560219]
[http://dx.doi.org/10.1136/gutjnl-2014-306996] [PMID: 24973316]
[http://dx.doi.org/10.1002/hep.22569] [PMID: 19030170]
[http://dx.doi.org/10.1007/s00535-012-0661-5] [PMID: 22965312]
[http://dx.doi.org/10.1016/j.ajpath.2012.06.010] [PMID: 22841474]
[http://dx.doi.org/10.1074/jbc.M116.773291] [PMID: 28536261]
[http://dx.doi.org/10.1111/jvh.12126] [PMID: 24383923]
[http://dx.doi.org/10.1128/JVI.03060-13] [PMID: 24429361]
[http://dx.doi.org/10.1007/s00441-011-1246-y] [PMID: 22006249]
[http://dx.doi.org/10.1002/hep.25613] [PMID: 22278637]
[http://dx.doi.org/10.1074/jbc.M113.517953] [PMID: 24196965]
[PMID: 18175267]
[http://dx.doi.org/10.1016/j.tox.2007.11.021] [PMID: 18291570]
[http://dx.doi.org/10.1073/pnas.0804549105] [PMID: 18663219]
[http://dx.doi.org/10.1371/journal.pone.0006229] [PMID: 19597549]
[http://dx.doi.org/10.1016/j.ygyno.2008.08.036] [PMID: 18954897]
[http://dx.doi.org/10.1016/j.taap.2016.07.008] [PMID: 27421576]
[http://dx.doi.org/10.1016/j.intimp.2016.09.011] [PMID: 27673475]
[http://dx.doi.org/10.1111/bcp.13282] [PMID: 28257154]
[http://dx.doi.org/10.1371/journal.pone.0179669] [PMID: 28678845]
[http://dx.doi.org/10.1089/aivt.2020.0008]
[http://dx.doi.org/10.1053/j.gastro.2020.01.052] [PMID: 32061595]
[http://dx.doi.org/10.1016/j.cmet.2018.10.012] [PMID: 30449681]
[http://dx.doi.org/10.1097/MOL.0000000000000420] [PMID: 28333713]
[http://dx.doi.org/10.1136/gutjnl-2015-310044] [PMID: 27436271]
[http://dx.doi.org/10.1186/s12864-018-4575-3] [PMID: 29523084]
[http://dx.doi.org/10.3390/ijms21186698] [PMID: 32933141]
[http://dx.doi.org/10.1136/gutjnl-2015-310822] [PMID: 27222533]
[http://dx.doi.org/10.3892/ijmm.2019.4375] [PMID: 31638173]
[http://dx.doi.org/10.1016/j.metabol.2019.01.018] [PMID: 30711569]
[http://dx.doi.org/10.1136/gutjnl-2014-308430] [PMID: 26282675]
[http://dx.doi.org/10.1016/j.jhep.2014.10.039] [PMID: 25450203]
[http://dx.doi.org/10.1136/gutjnl-2014-308883] [PMID: 26338827]
[http://dx.doi.org/10.3390/cancers13050940] [PMID: 33668153]
[http://dx.doi.org/10.1186/s12885-015-2007-1] [PMID: 26728044]
[http://dx.doi.org/10.4161/rna.18827] [PMID: 22258222]
[http://dx.doi.org/10.1016/j.cmet.2006.01.005] [PMID: 16459310]
[http://dx.doi.org/10.1111/liv.12429] [PMID: 24313922]
[http://dx.doi.org/10.1136/gutjnl-2018-318146] [PMID: 31300518]
[http://dx.doi.org/10.1111/obr.12765] [PMID: 30248223]
[http://dx.doi.org/10.1038/s41419-020-2293-7] [PMID: 32054840]
[http://dx.doi.org/10.1186/s10020-019-0085-2] [PMID: 31195981]
[http://dx.doi.org/10.1038/srep13729]
[http://dx.doi.org/10.1038/ncomms8466]
[http://dx.doi.org/10.1194/jlr.M071357] [PMID: 28250026]
[http://dx.doi.org/10.1038/s12276-021-00611-0] [PMID: 33879861]
[http://dx.doi.org/10.3390/ijms17101620] [PMID: 27669236]
[http://dx.doi.org/10.1039/D0FO02286A] [PMID: 33404569]
[http://dx.doi.org/10.1038/nrm3313] [PMID: 22436747]
[http://dx.doi.org/10.1371/journal.pone.0224820] [PMID: 31703079]
[http://dx.doi.org/10.1074/jbc.M114.602383] [PMID: 25118289]
[http://dx.doi.org/10.1152/ajpgi.00019.2012] [PMID: 22790595]
[http://dx.doi.org/10.1111/j.1530-0277.2007.00584.x] [PMID: 18162065]
[http://dx.doi.org/10.1111/j.1530-0277.2009.01007.x] [PMID: 19572984]
[http://dx.doi.org/10.4049/jimmunol.0901084] [PMID: 19783678]
[http://dx.doi.org/10.1155/2012/498232] [PMID: 22518321]
[http://dx.doi.org/10.1111/j.1530-0277.2009.01126.x] [PMID: 20102566]
[http://dx.doi.org/10.1186/s12967-015-0623-9] [PMID: 26264599]
[http://dx.doi.org/10.1074/jbc.M115.694133] [PMID: 26527689]
[http://dx.doi.org/10.1136/gutjnl-2015-311314] [PMID: 27196584]
[http://dx.doi.org/10.1074/jbc.M111.333534] [PMID: 22308024]
[http://dx.doi.org/10.1136/gutjnl-2016-311861] [PMID: 27679493]
[http://dx.doi.org/10.4103/1319-3767.96445] [PMID: 22626794]
[http://dx.doi.org/10.1016/j.jtcme.2017.07.002] [PMID: 29992106]
[http://dx.doi.org/10.1016/S0140-6736(08)60383-9] [PMID: 18328931]
[http://dx.doi.org/10.3390/ijms22158139] [PMID: 34360904]
[http://dx.doi.org/10.1016/j.cld.2008.07.001] [PMID: 18984474]
[http://dx.doi.org/10.1024/0300-9831/a000665] [PMID: 32686990]
[http://dx.doi.org/10.1371/journal.pone.0032999] [PMID: 22412969]
[http://dx.doi.org/10.1016/j.bbrc.2012.03.025] [PMID: 22446332]
[http://dx.doi.org/10.1371/journal.pone.0016081] [PMID: 21283674]
[http://dx.doi.org/10.1186/s13104-019-4227-y] [PMID: 30925941]
[http://dx.doi.org/10.1371/journal.pone.0108005] [PMID: 25303175]
[http://dx.doi.org/10.3390/jcm5030038] [PMID: 26999230]
[http://dx.doi.org/10.1016/j.biopha.2013.03.014] [PMID: 23643356]
[http://dx.doi.org/10.1089/ars.2016.6669] [PMID: 27502441]
[http://dx.doi.org/10.19082/1804] [PMID: 26955452]
[http://dx.doi.org/10.1371/journal.pone.0023937] [PMID: 21886843]
[http://dx.doi.org/10.1371/journal.pone.0255672] [PMID: 34506494]
[http://dx.doi.org/10.1172/JCI63455] [PMID: 22820290]
[http://dx.doi.org/10.3390/ijms17030280] [PMID: 26927063]
[http://dx.doi.org/10.1016/j.jhep.2018.12.016] [PMID: 30582979]
[http://dx.doi.org/10.3390/cells9081767] [PMID: 32717951]
[http://dx.doi.org/10.1038/s41419-018-0752-1] [PMID: 29915227]
[http://dx.doi.org/10.1371/journal.pone.0066577] [PMID: 23805240]
[http://dx.doi.org/10.3892/mmr.2015.3546] [PMID: 25815788]
[http://dx.doi.org/10.18632/oncotarget.23262] [PMID: 29416678]
[http://dx.doi.org/10.1016/j.jhep.2010.07.004] [PMID: 20800926]
[http://dx.doi.org/10.1093/cvr/cvr291] [PMID: 22038740]
[http://dx.doi.org/10.1002/hep.24441] [PMID: 21608007]
[http://dx.doi.org/10.1002/hep.24195] [PMID: 21520166]
[http://dx.doi.org/10.1016/j.bbrc.2012.12.071] [PMID: 23266610]
[http://dx.doi.org/10.1093/nar/gku260] [PMID: 24705650]
[http://dx.doi.org/10.1007/s11262-010-0555-7] [PMID: 21113793]
[http://dx.doi.org/10.1096/fj.11-187781] [PMID: 21903935]
[http://dx.doi.org/10.1093/nar/gkr067] [PMID: 21317190]
[http://dx.doi.org/10.1074/jbc.M113.458158] [PMID: 23649629]
[http://dx.doi.org/10.1002/jmv.23534] [PMID: 23532756]
[http://dx.doi.org/10.1016/j.bbrc.2010.07.021] [PMID: 20633528]
[PMID: 21725618]
[http://dx.doi.org/10.1016/j.bbrc.2011.06.191] [PMID: 21763284]
[http://dx.doi.org/10.1007/s00705-014-2208-y] [PMID: 25173609]
[http://dx.doi.org/10.1371/journal.pone.0034165] [PMID: 22479552]
[http://dx.doi.org/10.1111/jvh.12390] [PMID: 25720442]
[http://dx.doi.org/10.1261/rna.048744.114] [PMID: 25595716]
[http://dx.doi.org/10.1111/j.1365-2893.2011.01443.x] [PMID: 21692939]
[http://dx.doi.org/10.1007/s00430-011-0223-0] [PMID: 22392036]
[http://dx.doi.org/10.1126/science.1113329] [PMID: 16141076]
[http://dx.doi.org/10.1371/journal.pone.0047490] [PMID: 23091627]
[http://dx.doi.org/10.1111/j.1478-3231.2012.02795.x] [PMID: 22429613]
[http://dx.doi.org/10.3389/fimmu.2021.642958] [PMID: 33981303]
[http://dx.doi.org/10.1016/j.jff.2018.08.027]
[http://dx.doi.org/10.1016/j.addr.2014.10.029] [PMID: 25450260]
[http://dx.doi.org/10.1016/j.cell.2019.10.017] [PMID: 31730848]
[http://dx.doi.org/10.3389/fmed.2020.00007] [PMID: 32083086]
[http://dx.doi.org/10.1038/nature03677] [PMID: 15944709]
[http://dx.doi.org/10.1038/ng.2007.30] [PMID: 18066065]
[http://dx.doi.org/10.1016/j.molcel.2007.05.017] [PMID: 17540598]
[http://dx.doi.org/10.1016/j.jhep.2011.08.008] [PMID: 21888875]
[http://dx.doi.org/10.1002/hep.24614] [PMID: 22144109]
[http://dx.doi.org/10.1016/j.yexcr.2012.02.010] [PMID: 22387901]
[http://dx.doi.org/10.1097/MCG.0b013e3181f18ac2] [PMID: 21278583]
[http://dx.doi.org/10.1111/j.1440-1827.2010.02526.x] [PMID: 20518884]
[http://dx.doi.org/10.1016/j.biocel.2009.02.021] [PMID: 20619223]
[http://dx.doi.org/10.1002/hep.24538] [PMID: 22045675]
[http://dx.doi.org/10.3892/mmr.2012.838] [PMID: 22427142]
[http://dx.doi.org/10.1177/0192623312464436] [PMID: 23143187]
[http://dx.doi.org/10.1016/j.cca.2013.05.021] [PMID: 23727030]
[http://dx.doi.org/10.1371/journal.pone.0153497] [PMID: 27077736]
[http://dx.doi.org/10.1038/ijo.2017.21] [PMID: 28119530]
[http://dx.doi.org/10.1053/j.gastro.2007.05.022] [PMID: 17681183]
[http://dx.doi.org/10.1038/sj.onc.1210856] [PMID: 17968323]
[http://dx.doi.org/10.1002/ijc.23693] [PMID: 18649363]
[http://dx.doi.org/10.1038/onc.2009.211] [PMID: 19617899]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0092] [PMID: 19671867]
[http://dx.doi.org/10.1056/NEJMoa0901282] [PMID: 19812400]
[http://dx.doi.org/10.1002/hep.22806] [PMID: 19296470]
[http://dx.doi.org/10.1038/ng.392] [PMID: 19483683]
[http://dx.doi.org/10.1002/hep.23008] [PMID: 19472311]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1840] [PMID: 20103675]
[http://dx.doi.org/10.1002/hep.23443] [PMID: 20054866]
[http://dx.doi.org/10.1038/sj.bjc.6606010] [PMID: 21102580]
[http://dx.doi.org/10.1002/ijc.25336] [PMID: 20309945]
[http://dx.doi.org/10.1038/ajg.2011.161] [PMID: 21606975]
[http://dx.doi.org/10.1002/hep.24243] [PMID: 21400558]
[http://dx.doi.org/10.1002/hep.25984] [PMID: 22821679]
[http://dx.doi.org/10.1038/s12276-018-0153-7] [PMID: 30258086]
[http://dx.doi.org/10.1016/j.jaut.2009.02.022] [PMID: 19345069]
[http://dx.doi.org/10.3168/jds.2018-14785] [PMID: 30197143]
[http://dx.doi.org/10.3390/ijms21197368] [PMID: 33036164]
[http://dx.doi.org/10.1039/C4OB02104E] [PMID: 25574760]
[http://dx.doi.org/10.1016/j.snb.2018.09.058]
[http://dx.doi.org/10.1039/C7AN02001E] [PMID: 29560992]
[http://dx.doi.org/10.1007/s00216-017-0632-z] [PMID: 29032457]
[http://dx.doi.org/10.1016/j.jbiotec.2017.10.003] [PMID: 29017848]
[http://dx.doi.org/10.1007/s00216-009-2744-6] [PMID: 19367400]
[http://dx.doi.org/10.1007/s11033-012-2442-x] [PMID: 23307300]
[http://dx.doi.org/10.1016/j.jpha.2019.05.004] [PMID: 31452959]
[http://dx.doi.org/10.1371/journal.pcbi.1007209] [PMID: 31329575]
[http://dx.doi.org/10.1093/bib/bbaa186]
[http://dx.doi.org/10.1093/bib/bbz159] [PMID: 31927572]
[http://dx.doi.org/10.1016/j.jhep.2014.10.004] [PMID: 25308172]
[http://dx.doi.org/10.1136/gutjnl-2020-322526] [PMID: 33127832]