1 1021 86 CIRCULAR RNA AS AN EPIGENETIC REGULATOR IN CHRONIC LIVER DISEASES. CIRCULAR RNA (CIRCRNA) IS A TYPE OF NON-CODING RNA CHARACTERIZED BY A COVALENTLY CLOSED CONTINUOUS LOOP. CIRCRNA IS GENERATED BY PRE-MRNA THROUGH BACK-SPLICING AND IS PROBABLY CLEARED UP BY EXTRACELLULAR VESICLES. CIRCRNAS PLAY A PIVOTAL ROLE IN THE EPIGENETIC REGULATION OF GENE EXPRESSION AT TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL LEVELS. RECENTLY, CIRCRNAS HAVE BEEN DEMONSTRATED TO BE INVOLVED IN THE REGULATION OF LIVER HOMEOSTASIS AND DISEASES. HOWEVER, THE EPIGENETIC ROLE AND UNDERLYING MECHANISMS OF CIRCRNAS IN CHRONIC LIVER DISEASES REMAIN UNCLEAR. THIS REVIEW DISCUSSED THE ROLE OF CIRCRNAS IN NON-NEOPLASTIC CHRONIC LIVER DISEASES, INCLUDING ALCOHOLIC LIVER DISEASE (ALD), METABOLIC-ASSOCIATED FATTY LIVER DISEASE (MAFLD), VIRAL HEPATITIS, LIVER INJURY AND REGENERATION, LIVER CIRRHOSIS, AND AUTOIMMUNE LIVER DISEASE. THE REVIEW ALSO HIGHLIGHTED THAT FURTHER EFFORTS ARE URGENTLY NEEDED TO DEVELOP CIRCRNAS AS NOVEL DIAGNOSTICS AND THERAPEUTICS FOR CHRONIC LIVER DISEASES. 2021 2 6092 37 THE EFFECTS OF EPIGENETIC MODIFICATION ON THE OCCURRENCE AND PROGRESSION OF LIVER DISEASES AND THE INVOLVED MECHANISM. INTRODUCTION: EPIGENETIC MODIFICATION IS A TYPE OF GENE EXPRESSION AND REGULATION THAT DOES NOT INVOLVE CHANGES IN DNA SEQUENCES. AN INCREASING NUMBER OF STUDIES HAVE PROVEN THAT EPIGENETIC MODIFICATIONS PLAY AN IMPORTANT ROLE IN THE OCCURRENCE AND PROGRESSION OF LIVER DISEASES THROUGH THE GENE REGULATION AND PROTEIN EXPRESSIONS OF HEPATOCELLULAR LIPID METABOLISM, INFLAMMATORY REACTION, CELL PROLIFERATION, AND ACTIVATION, ETC.AREAS COVERED: IN THIS STUDY, WE ELABORATED AND ANALYZED THE UNDERLYING FUNCTIONAL MECHANISM OF EPIGENETIC MODIFICATION IN ALCOHOLIC LIVER DISEASE (ALD), NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), LIVER FIBROSIS (LF), VIRAL HEPATITIS, HEPATOCELLULAR CARCINOMA (HCC), AND RESEARCH PROGRESS OF RECENT YEARS.EXPERT OPINION: THE FURTHER UNDERSTANDING OF EPIGENETIC MECHANISMS THAT CAN REGULATE GENE EXPRESSION AND CELL PHENOTYPE LEADS TO NEW INSIGHTS IN EPIGENETIC CONTROL OF CHRONIC LIVER DISEASE. CURRENTLY, HEPATOLOGISTS ARE EXPLORING THE ROLE OF DNA METHYLATION, HISTONE/CHROMATIN MODIFICATION, AND NON-CODING RNA IN SPECIFIC LIVER PATHOLOGY. THESE FINDINGS HAVE LED TO ADVANCES IN DIRECT EPIGENETIC BIOMARKER TESTING OF PATIENT TISSUE OR BODY FLUID SPECIMENS, AS WELL AS QUANTITATIVE ANALYSIS. BASED ON THESE FINDINGS, DRUG VALIDATION OF SOME TARGETS INVOLVED IN THE EPIGENETIC MECHANISM OF LIVER DISEASE IS GRADUALLY BEING CARRIED OUT CLINICALLY. 2020 3 2341 25 EPIGENETIC REGULATION OF LIVER FIBROSIS. FIBROSIS IS A COMMON AND IMPORTANT PATHOLOGY ASSOCIATED WITH PROGRESSIVE CHRONIC LIVER DISEASES AND UNDERLIES THE DEVELOPMENT OF CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. RESEARCH INTO THE MOLECULAR REGULATION OF FIBROSIS HAS DISCOVERED THAT IT IS UNDER THE CONTROL OF A NUMBER OF EPIGENETIC MECHANISMS INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS AND THE ACTIVITIES OF NON-CODING RNAS. A DEEPER UNDERSTANDING OF HOW EPIGENETIC REGULATORS SUCH AS DNA METHYLTRANSERASES, METHYL-DNA BINDING PROTEINS, HISTONE MODIFYING ENZYMES AND REGULATORY RNA MOLECULES IMPACT ON THE FIBROGENIC PROCESS IS EXPECTED TO RESULT IN NEW BIOMARKERS FOR DISEASE PROGRESSION AS WELL AS NOVEL THERAPEUTIC TARGETS. THE AIM OF THIS MINI-REVIEW IS TO BRIEFLY INTRODUCE THE READER TO THE MAJOR EPIGENETIC REGULATORS SO FAR IDENTIFIED AS BEING IMPLICATED IN FIBROSIS. 2015 4 4722 27 NONCODING RNAS IN NONALCOHOLIC FATTY LIVER DISEASE: POTENTIAL DIAGNOSIS AND PROGNOSIS BIOMARKERS. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS CURRENTLY THE MOST COMMON CHRONIC LIVER DISEASE WORLDWIDE IN PART DUE TO THE CONCOMITANT OBESITY PANDEMIC AND INSULIN RESISTANCE (IR). IT IS INCREASINGLY BECOMING EVIDENT THAT NAFLD IS A DISEASE AFFECTING NUMEROUS EXTRAHEPATIC VITAL ORGANS AND REGULATORY PATHWAYS. THE MOLECULAR MECHANISMS UNDERLYING THE NONALCOHOLIC STEATOSIS FORMATION ARE POORLY UNDERSTOOD, AND LITTLE INFORMATION IS AVAILABLE ON THE PATHWAYS THAT ARE RESPONSIBLE FOR THE PROGRESSIVE HEPATOCELLULAR DAMAGE THAT FOLLOWS LIPID ACCUMULATION. RECENTLY, MUCH RESEARCH HAS FOCUSED ON THE IDENTIFICATION OF THE EPIGENETIC MODIFICATIONS THAT CONTRIBUTE TO NAFLD PATHOGENESIS. NONCODING RNAS (NCRNAS) ARE ONE OF SUCH EPIGENETIC FACTORS THAT COULD BE IMPLICATED IN THE NAFLD DEVELOPMENT AND PROGRESSION. IN THIS REVIEW, WE SUMMARIZE THE CURRENT KNOWLEDGE OF THE GENETIC AND EPIGENETIC FACTORS POTENTIALLY UNDERLYING THE DISEASE. PARTICULAR EMPHASIS WILL BE PUT ON THE CONTRIBUTION OF MICRORNAS (MIRNAS), LONG NONCODING RNAS (LNCRNAS), AND CIRCULAR RNAS (CIRCRNAS) TO THE PATHOPHYSIOLOGY OF NAFLD AS WELL AS THEIR POTENTIAL USE AS THERAPEUTIC TARGETS OR AS MARKERS FOR THE PREDICTION AND THE PROGRESSION OF THE DISEASE. 2020 5 2014 28 EPIGENETIC BIOMARKERS FOR THE DIAGNOSIS AND TREATMENT OF LIVER DISEASE. RESEARCH IN THE LAST DECADES HAS DEMONSTRATED THE RELEVANCE OF EPIGENETICS IN CONTROLLING GENE EXPRESSION TO MAINTAIN CELL HOMEOSTASIS, AND THE IMPORTANT ROLE PLAYED BY EPIGENOME ALTERATIONS IN DISEASE DEVELOPMENT. MOREOVER, THE REVERSIBILITY OF EPIGENETIC MARKS CAN BE HARNESSED AS A THERAPEUTIC STRATEGY, AND EPIGENETIC MARKS CAN BE USED AS DIAGNOSIS BIOMARKERS. EPIGENETIC ALTERATIONS IN DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATIONS (PTMS), AND NON-CODING RNA (NCRNA) EXPRESSION HAVE BEEN ASSOCIATED WITH THE PROCESS OF HEPATOCARCINOGENESIS. HERE, WE SUMMARIZE EPIGENETIC ALTERATIONS INVOLVED IN THE PATHOGENESIS OF CHRONIC LIVER DISEASE (CLD), PARTICULARLY FOCUSING ON DNA METHYLATION. WE ALSO DISCUSS THEIR UTILITY AS EPIGENETIC BIOMARKERS IN LIQUID BIOPSY FOR THE DIAGNOSIS AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA (HCC). FINALLY, WE DISCUSS THE POTENTIAL OF EPIGENETIC THERAPEUTIC STRATEGIES FOR HCC TREATMENT. 2021 6 5495 34 REVIEW ON CIRCULAR RNAS AND NEW INSIGHTS INTO THEIR ROLES IN CANCER. CIRCULAR RNAS (CIRCRNAS) ARE A VERY INTERESTING CLASS OF CONSERVED SINGLE-STRANDED RNA MOLECULES DERIVED FROM EXONIC OR INTRONIC SEQUENCES BY PRECURSOR MRNA BACK-SPLICING. UNLIKE CANONICAL LINEAR RNAS, CIRCRNAS FORM COVALENTLY CLOSED, CONTINUOUS STABLE LOOPS WITHOUT A 5'END CAP AND 3'END POLY(A) TAIL, AND THEREFORE ARE RESISTANT TO EXONUCLEASE DIGESTION. THE MAJORITY OF CIRCRNAS ARE HIGHLY ABUNDANT, AND CONSERVED ACROSS DIFFERENT SPECIES WITH A TISSUE OR DEVELOPMENTAL-STAGE-SPECIFIC EXPRESSION. CIRCRNAS HAVE BEEN SHOWN TO PLAY IMPORTANT ROLES AS MICRORNA SPONGES, REGULATORS OF GENE SPLICING AND TRANSCRIPTION, RNA-BINDING PROTEIN SPONGES AND PROTEIN/PEPTIDE TRANSLATORS. EMERGING EVIDENCE REVEALS THAT CIRCRNAS FUNCTION IN VARIOUS HUMAN DISEASES, PARTICULARLY CANCERS, AND MAY FUNCTION AS BETTER PREDICTIVE BIOMARKERS AND THERAPEUTIC TARGETS FOR CANCER TREATMENT. IN CONSIDERATION OF THEIR POTENTIAL CLINICAL RELEVANCE, CIRCRNAS HAVE BECOME A NEW RESEARCH HOTSPOT IN THE FIELD OF TUMOR PATHOLOGY. IN THE PRESENT STUDY, THE CURRENT UNDERSTANDING OF THE BIOGENESIS, CHARACTERISTICS, DATABASES, RESEARCH METHODS, BIOLOGICAL FUNCTIONS SUBCELLULAR DISTRIBUTION, EPIGENETIC REGULATION, EXTRACELLULAR TRANSPORT AND DEGRADATION OF CIRCRNAS WAS DISCUSSED. IN PARTICULAR, THE MULTIPLE DATABASES AND METHODS INVOLVED IN CIRCRNA RESEARCH WERE FIRST SUMMARIZED, AND THE RECENT ADVANCES IN DETERMINING THE POTENTIAL ROLES OF CIRCRNAS IN TUMOR GROWTH, MIGRATION AND INVASION, WHICH RENDER CIRCRNAS BETTER PREDICTIVE BIOMARKERS, WERE DESCRIBED. FURTHERMORE, FUTURE PERSPECTIVES FOR THE CLINICAL APPLICATION OF CIRCRNAS IN THE MANAGEMENT OF PATIENTS WITH CANCER WERE PROPOSED, WHICH COULD PROVIDE NEW INSIGHTS INTO CIRCRNAS IN THE FUTURE. 2021 7 4720 30 NONCODING RNAS AS ADDITIONAL MEDIATORS OF EPIGENETIC REGULATION IN NONALCOHOLIC FATTY LIVER DISEASE. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) HAS EMERGED AS THE MOST COMMON CAUSE OF CHRONIC LIVER DISORDER WORLDWIDE. IT REPRESENTS A SPECTRUM THAT INCLUDES A CONTINUUM OF DIFFERENT CLINICAL ENTITIES RANGING FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS, WHICH CAN EVOLVE TO CIRRHOSIS AND IN SOME CASES TO HEPATOCELLULAR CARCINOMA, ULTIMATELY LEADING TO LIVER FAILURE. THE PATHOGENESIS OF NAFLD AND THE MECHANISMS UNDERLYING ITS PROGRESSION TO MORE PATHOLOGICAL STAGES ARE NOT COMPLETELY UNDERSTOOD. BESIDES GENETIC FACTORS, EVIDENCE INDICATES THAT EPIGENETIC MECHANISMS OCCURRING IN RESPONSE TO ENVIRONMENTAL STIMULI ALSO CONTRIBUTE TO THE DISEASE RISK. NONCODING RNAS (NCRNAS), INCLUDING MICRORNAS, LONG NONCODING RNAS, AND CIRCULAR RNAS, ARE ONE OF THE EPIGENETIC FACTORS THAT PLAY KEY REGULATORY ROLES IN THE DEVELOPMENT OF NAFLD. AS THE FIELD OF NCRNAS IS RAPIDLY EVOLVING, THE PRESENT REVIEW AIMS TO EXPLORE THE CURRENT STATE OF KNOWLEDGE ON THE ROLES OF THESE RNA SPECIES IN THE PATHOGENESIS OF NAFLD, HIGHLIGHT RELEVANT MECHANISMS BY WHICH SOME NCRNAS CAN MODULATE REGULATORY NETWORKS IMPLICATED IN NAFLD, AND DISCUSS KEY CHALLENGES AND FUTURE DIRECTIONS FACING CURRENT RESEARCH IN THE HOPES OF DEVELOPING NCRNAS AS NEXT-GENERATION NON-INVASIVE DIAGNOSTICS AND THERAPIES IN NAFLD AND SUBSEQUENT PROGRESSION TO HEPATOCELLULAR CARCINOMA. 2022 8 5533 30 ROLE AND MECHANISM OF DNA METHYLATION AND ITS INHIBITORS IN HEPATIC FIBROSIS. LIVER FIBROSIS IS A REPAIR RESPONSE TO INJURY CAUSED BY VARIOUS CHRONIC STIMULI THAT CONTINUALLY ACT ON THE LIVER. AMONG THEM, THE ACTIVATION OF HEPATIC STELLATE CELLS (HSCS) AND THEIR TRANSFORMATION INTO A MYOFIBROBLAST PHENOTYPE IS A KEY EVENT LEADING TO LIVER FIBROSIS, HOWEVER THE MECHANISM HAS NOT YET BEEN ELUCIDATED. THE MOLECULAR BASIS OF HSC ACTIVATION INVOLVES CHANGES IN THE REGULATION OF GENE EXPRESSION WITHOUT CHANGES IN THE GENOME SEQUENCE, NAMELY, VIA EPIGENETIC REGULATION. DNA METHYLATION IS A KEY FOCUS OF EPIGENETIC RESEARCH, AS IT AFFECTS THE EXPRESSION OF FIBROSIS-RELATED, METABOLISM-RELATED, AND TUMOR SUPPRESSOR GENES. INCREASING STUDIES HAVE SHOWN THAT DNA METHYLATION IS CLOSELY RELATED TO SEVERAL PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES INCLUDING HSC ACTIVATION AND LIVER FIBROSIS. THIS REVIEW AIMED TO DISCUSS THE MECHANISM OF DNA METHYLATION IN THE PATHOGENESIS OF LIVER FIBROSIS, EXPLORE DNA METHYLATION INHIBITORS AS POTENTIAL THERAPIES FOR LIVER FIBROSIS, AND PROVIDE NEW INSIGHTS ON THE PREVENTION AND CLINICAL TREATMENT OF LIVER FIBROSIS. 2023 9 4335 33 MICRORNAS: SMALL MOLECULES WITH SIGNIFICANT FUNCTIONS, PARTICULARLY IN THE CONTEXT OF VIRAL HEPATITIS B AND C INFECTION. A MICRORNA (MIRNA) IS DEFINED AS A SMALL MOLECULE OF NON-CODING RNA (NCRNA). ITS MOLECULAR SIZE IS ABOUT 20 NUCLEOTIDES (NT), AND IT ACTS ON GENE EXPRESSION'S REGULATION AT THE POST-TRANSCRIPTION LEVEL THROUGH BINDING TO THE 3'UNTRANSLATED REGIONS (UTR), CODING SEQUENCES, OR 5'UTR OF THE TARGET MESSENGER RNAS (MRNAS), WHICH LEADS TO THE SUPPRESSION OR DEGRADATION OF THE MRNA. IN RECENT YEARS, A HUGE EVOLUTION HAS IDENTIFIED THE ORIGIN AND FUNCTION OF MIRNAS, FOCUSING ON THEIR IMPORTANT EFFECTS IN RESEARCH AND CLINICAL APPLICATIONS. FOR EXAMPLE, MICRORNAS ARE KEY PLAYERS IN HCV INFECTION AND HAVE IMPORTANT HOST CELLULAR FACTORS REQUIRED FOR HCV REPLICATION AND CELL GROWTH. ALTERED EXPRESSION OF MIRNAS AFFECTS THE PATHOGENICITY ASSOCIATED WITH HCV INFECTION THROUGH REGULATING DIFFERENT SIGNALING PATHWAYS THAT CONTROL HCV/IMMUNITY INTERACTIONS, PROLIFERATION, AND CELL DEATH. ON THE OTHER HAND, CIRCULATING MIRNAS CAN BE USED AS NOVEL BIOMARKERS AND DIAGNOSTIC TOOLS FOR HCV PATHOGENESIS AND EARLY THERAPEUTIC RESPONSE. MOREOVER, MICRORNAS (MIRNA) HAVE BEEN INVOLVED IN HEPATITIS B VIRUS (HBV) GENE EXPRESSION AND ADVANCED ANTIVIRAL DISCOVERY. THEY REGULATE HBV/HCV REPLICATION AND PATHOGENESIS WITH DIFFERENT PATHWAYS INVOLVING FACILITATION, INHIBITION, ACTIVATION OF THE IMMUNE SYSTEM (INNATE AND ADAPTIVE), AND EPIGENETIC MODIFICATIONS. IN THIS SHORT REVIEW, WE WILL DISCUSS HOW MICRORNAS CAN BE USED AS PROGNOSTIC, DIAGNOSTIC, AND THERAPEUTIC TOOLS, ESPECIALLY FOR CHRONIC HEPATITIS VIRUSES (HBV AND HCV), AS WELL AS HOW THEY COULD BE USED AS NEW BIOMARKERS DURING INFECTION AND ADVANCED TREATMENT. 2023 10 1020 29 CIRCRNAS IN ATHEROSCLEROSIS, WITH SPECIAL EMPHASIS ON THE SPONGY EFFECT OF CIRCRNAS ON MIRNAS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE, WHICH LEADS TO ATHEROSCLEROTIC RUPTURE, LUMEN STENOSIS AND THROMBOSIS, AND OFTEN ENDANGERS LIFE. CIRCULAR RNAS (CIRCRNAS) ARE A SPECIAL CLASS OF NON-CODING RNA MOLECULES, WHOSE ABNORMAL EXPRESSION HAS BEEN PROVED TO BE CLOSELY RELATED TO HUMAN DISEASES, INCLUDING AS. BOTH THE ABNORMAL REGULATION OF CIRCRNAS AND THE SPONGING EFFECT ON MIRNAS WOULD LEAD TO CHANGES IN GENE EXPRESSION IN THE FORM OF EPIGENETIC MODIFICATION, ULTIMATELY LEADING TO THE FORMATION OF AS. CIRCRNAS CAN BE USED AS PERIPHERAL BLOOD MARKERS OF AS, AND PLAY AN IMPORTANT REGULATORY ROLE IN THE PROLIFERATION, MIGRATION, INFLAMMATION AND APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS, ENDOTHELIAL CELLS AND MACROPHAGE, WHICH ARE KEY CELLS FOR THE DEVELOPMENT OF AS. THE IN-DEPTH UNDERSTANDING OF CIRCRNAS IN AS NOT ONLY PROVIDES A NEW METHOD FOR THE DIAGNOSIS OF AS, BUT ALSO PROVIDES A NEW IDEA FOR THE TREATMENT OF AS. 2023 11 4104 32 MECHANISM AND THERAPEUTIC OPPORTUNITIES OF HISTONE MODIFICATIONS IN CHRONIC LIVER DISEASE. CHRONIC LIVER DISEASE (CLD) REPRESENTS A GLOBAL HEALTH PROBLEM, ACCOUNTING FOR THE HEAVY BURDEN OF DISABILITY AND INCREASED HEALTH CARE UTILIZATION. EPIGENOME ALTERATIONS PLAY AN IMPORTANT ROLE IN THE OCCURRENCE AND PROGRESSION OF CLD. HISTONE MODIFICATIONS, WHICH INCLUDE ACETYLATION, METHYLATION, AND PHOSPHORYLATION, REPRESENT AN ESSENTIAL PART OF EPIGENETIC MODIFICATIONS THAT AFFECT THE TRANSCRIPTIONAL ACTIVITY OF GENES. DIFFERENT FROM GENETIC MUTATIONS, HISTONE MODIFICATIONS ARE PLASTIC AND REVERSIBLE. THEY CAN BE MODULATED PHARMACOLOGICALLY WITHOUT CHANGING THE DNA SEQUENCE. THUS, THERE MIGHT BE CHANCES TO ESTABLISH INTERVENTIONAL SOLUTIONS BY TARGETING HISTONE MODIFICATIONS TO REVERSE CLD. HERE WE SUMMARIZED THE ROLES OF HISTONE MODIFICATIONS IN THE CONTEXT OF ALCOHOLIC LIVER DISEASE (ALD), METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD), VIRAL HEPATITIS, AUTOIMMUNE LIVER DISEASE, DRUG-INDUCED LIVER INJURY (DILI), AND LIVER FIBROSIS OR CIRRHOSIS. THE POTENTIAL TARGETS OF HISTONE MODIFICATIONS FOR TRANSLATION INTO THERAPEUTICS WERE ALSO INVESTIGATED. IN PROSPECT, HIGH EFFICACY AND LOW TOXICITY DRUGS THAT ARE SELECTIVELY TARGETING HISTONE MODIFICATIONS ARE REQUIRED TO COMPLETELY REVERSE CLD AND PREVENT THE DEVELOPMENT OF LIVER CIRRHOSIS AND MALIGNANCY. 2021 12 1051 31 CLINICAL IMPLICATIONS OF EXOSOME-DERIVED NONCODING RNAS IN LIVER. EXOSOMES, ONE OF THREE MAIN TYPES OF EXTRACELLULAR VESICLES, ARE ~30-100 NM IN DIAMETER AND HAVE A LIPID BILAYER MEMBRANE. THEY ARE WIDELY DISTRIBUTED IN ALMOST ALL BODY FLUIDS. EXOSOMES HAVE THE POTENTIAL TO REGULATE UNKNOWN CELLULAR AND MOLECULAR MECHANISMS IN INTERCELLULAR COMMUNICATION, ORGAN HOMEOSTASIS, AND DISEASES. THEY ARE CRITICAL SIGNAL CARRIERS THAT TRANSFER NUCLEIC ACIDS, PROTEINS, LIPIDS, AND OTHER SUBSTANCES INTO RECIPIENT CELLS, PARTICIPATING IN CELLULAR SIGNAL TRANSDUCTION AND MATERIAL EXCHANGE. NCRNAS ARE NON-PROTEIN-CODING GENES THAT ACCOUNT FOR OVER 90% OF THE GENOME AND INCLUDE MICRORNAS (MIRNAS), LONG NCRNAS (LNCRNAS), AND CIRCULAR RNAS (CIRCRNAS). NCRNAS ARE CRUCIAL FOR PHYSIOLOGICAL AND PATHOLOGICAL ACTIVITIES IN THE LIVER BY PARTICIPATING IN GENE TRANSCRIPTION, POSTTRANSCRIPTIONAL EPIGENETIC REGULATION, AND CELLULAR PROCESSES THROUGH INTERACTING WITH DNA, RNA, OR PROTEINS. RECENT EVIDENCE FROM BOTH CLINICAL AND PRECLINICAL STUDIES INDICATES THAT EXOSOME-DERIVED NONCODING RNAS (NCRNAS) ARE HIGHLY INVOLVED IN THE PROGRESSION OF ACUTE AND CHRONIC LIVER DISEASES BY REGULATING HEPATIC LIPID METABOLISM, INNATE IMMUNITY, VIRAL INFECTION, FIBROSIS, AND CANCER. THEREFORE, EXOSOME-DERIVED NCRNAS HAVE PROMISING POTENTIAL AND CLINICAL IMPLICATIONS FOR THE EARLY DIAGNOSIS, TARGETED THERAPY, AND PROGNOSIS OF LIVER DISEASES. 2022 13 6106 24 THE EMERGING ROLE OF MICRORNAS IN NAFLD: HIGHLIGHT OF MICRORNA-29A IN MODULATING OXIDATIVE STRESS, INFLAMMATION, AND BEYOND. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS A COMMON CAUSE OF CHRONIC LIVER DISEASE AND RANGES FROM STEATOSIS TO STEATOHEPATITIS AND TO LIVER FIBROSIS. LIPOTOXICITY IN HEPATOCYTES, ELEVATED OXIDATIVE STRESS AND THE ACTIVATION OF PROINFLAMMATORY MEDIATORS OF KUPFFER CELLS, AND FIBROGENIC PATHWAYS OF ACTIVATED HEPATIC STELLATE CELLS CAN CONTRIBUTE TO THE DEVELOPMENT OF NAFLD. MICRORNAS (MIRS) PLAY A CRUCIAL ROLE IN THE DYSREGULATED METABOLISM AND INFLAMMATORY SIGNALING CONNECTED WITH NAFLD AND ITS PROGRESSION TOWARDS MORE SEVERE STAGES. OF NOTE, THE PROTECTIVE EFFECT OF NON-CODING MIR-29A ON LIVER DAMAGE AND ITS VERSATILE ACTION ON EPIGENETIC ACTIVITY, MITOCHONDRIAL HOMEOSTASIS AND IMMUNOMODULATION MAY IMPROVE OUR PERCEPTION OF THE PATHOGENESIS OF NAFLD. HEREIN, WE REVIEW THE BIOLOGICAL FUNCTIONS OF CRITICAL MIRS IN NAFLD, AS WELL AS HIGHLIGHT THE EMERGING ROLE OF MIR-29A IN THERAPEUTIC APPLICATION AND THE RECENT ADVANCES IN MOLECULAR MECHANISMS UNDERLYING ITS LIVER PROTECTIVE EFFECT. 2020 14 4369 26 MIRNAS AND NAFLD: FROM PATHOPHYSIOLOGY TO THERAPY. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ASSOCIATED WITH A THOROUGH REPROGRAMMING OF HEPATIC METABOLISM. EPIGENETIC MECHANISMS, IN PARTICULAR THOSE ASSOCIATED WITH DEREGULATION OF THE EXPRESSIONS AND ACTIVITIES OF MICRORNAS (MIRNAS), PLAY A MAJOR ROLE IN METABOLIC DISORDERS ASSOCIATED WITH NAFLD AND THEIR PROGRESSION TOWARDS MORE SEVERE STAGES OF THE DISEASE. IN THIS REVIEW, WE DISCUSS THE RECENT PROGRESS ADDRESSING THE ROLE OF THE MANY FACETS OF COMPLEX MIRNA REGULATORY NETWORKS IN THE DEVELOPMENT AND PROGRESSION OF NAFLD. THE BASIC CONCEPTS AND MECHANISMS OF MIRNA-MEDIATED GENE REGULATION AS WELL AS THE VARIOUS SETBACKS ENCOUNTERED IN BASIC AND TRANSLATIONAL RESEARCH IN THIS FIELD ARE DEBATED. MIRNAS IDENTIFIED SO FAR, WHOSE EXPRESSIONS/ACTIVITIES ARE DEREGULATED IN NAFLD, AND WHICH CONTRIBUTE TO THE OUTCOMES OF THIS PATHOLOGY ARE FURTHER REVIEWED. FINALLY, THE POTENTIAL THERAPEUTIC USAGES IN A SHORT TO MEDIUM TERM OF MIRNA-BASED STRATEGIES IN NAFLD, IN PARTICULAR TO IDENTIFY NON-INVASIVE BIOMARKERS, OR TO DESIGN PHARMACOLOGICAL ANALOGUES/INHIBITORS HAVING A BROAD RANGE OF ACTIONS ON HEPATIC METABOLISM, ARE HIGHLIGHTED. 2019 15 3250 31 HEPATITIS B VIRUS INFECTION, MICRORNAS AND LIVER DISEASE. HEPATITIS B VIRUS (HBV) ATTACKS THE LIVER AND CAN CAUSE BOTH ACUTE AS WELL AS CHRONIC LIVER DISEASES WHICH MIGHT LEAD TO LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. REGARDLESS OF THE AVAILABILITY OF A VACCINE AND NUMEROUS TREATMENT OPTIONS, HBV IS A MAJOR CAUSE OF MORBIDITY AND MORTALITY ACROSS THE WORLD. RECENTLY,MICRORNAS (MIRNAS) HAVE EMERGED AS IMPORTANT MODULATORS OF GENE FUNCTION. STUDIES ON THE ROLE OF MIRNA IN THE REGULATION OF HEPATITIS B VIRUS GENE EXPRESSION HAVE BEEN THE FOCUS OF MODERN ANTIVIRAL RESEARCH. MIRNAS CAN REGULATE VIRAL REPLICATION AND PATHOGENESIS IN A NUMBER OF DIFFERENT WAYS, WHICH INCLUDEFACILITATION, DIRECT OR INDIRECT INHIBITION, ACTIVATION OF IMMUNE RESPONSE, EPIGENETIC MODULATION, ETC. NEVERTHELESS, THESE MECHANISMS CAN APPROPRIATELY BE USED WITH A DIAGNOSTICAND/OR THERAPEUTIC APPROACH. THE PRESENT REVIEW IS AN ATTEMPT TO CLASSIFY SPECIFIC MIRNAS THAT ARE REPORTED TO BE ASSOCIATED WITH VARIOUS ASPECTS OF HEPATITIS B BIOLOGY, IN ORDER TO PRECISELY PRESENT THE PARTICIPATION OF INDIVIDUAL MIRNAS IN MULTIPLE ASPECTS RELATING TO HBV. 2015 16 2323 22 EPIGENETIC REGULATION OF HEPATIC STELLATE CELL ACTIVATION AND MACROPHAGE IN CHRONIC LIVER INFLAMMATION. CHRONIC LIVER INFLAMMATION IS A COMPLEX PATHOLOGICAL PROCESS UNDER DIFFERENT STRESS CONDITIONS, AND THE ROLES OF STELLATE CELLS AND MACROPHAGES IN CHRONIC LIVER INFLAMMATION HAVE BEEN WIDELY REPORTED. MODERATE LIVER INFLAMMATION CAN PROTECT THE LIVER FROM DAMAGE AND FACILITATE THE RECOVERY OF LIVER INJURY. HOWEVER, AN INFLAMMATORY RESPONSE THAT IS TOO INTENSE CAN RESULT IN MASSIVE DEATH OF HEPATOCYTES, WHICH LEADS TO IRREVERSIBLE DAMAGE TO THE LIVER PARENCHYMA. EPIGENETIC REGULATION PLAYS A KEY PART IN LIVER INFLAMMATION. THIS STUDY REVIEWS THE REGULATION OF EPIGENETICS ON STELLATE CELLS AND MACROPHAGES TO EXPLORE THE NEW MECHANISMS OF EPIGENETICS ON LIVER INFLAMMATION AND PROVIDE NEW IDEAS FOR THE TREATMENT OF LIVER DISEASE. 2021 17 2544 24 EPIGENETICS IN LIVER DISEASE: FROM BIOLOGY TO THERAPEUTICS. KNOWLEDGE OF THE FUNDAMENTAL EPIGENETIC MECHANISMS GOVERNING GENE EXPRESSION AND CELLULAR PHENOTYPE ARE SUFFICIENTLY ADVANCED THAT NOVEL INSIGHTS INTO THE EPIGENETIC CONTROL OF CHRONIC LIVER DISEASE ARE NOW EMERGING. HEPATOLOGISTS ARE IN THE PROCESS OF SHEDDING LIGHT ON THE ROLES PLAYED BY DNA METHYLATION, HISTONE/CHROMATIN MODIFICATIONS AND NON-CODING RNAS IN SPECIFIC LIVER PATHOLOGIES. ALONGSIDE THESE DISCOVERIES ARE ADVANCES IN THE TECHNOLOGIES FOR THE DETECTION AND QUANTIFICATION OF EPIGENETIC BIOMARKERS, EITHER DIRECTLY FROM PATIENT TISSUE OR FROM BODY FLUIDS. THE PREMISE FOR THIS REVIEW IS TO SURVEY THE RECENT ADVANCES IN THE FIELD OF LIVER EPIGENETICS AND TO EXPLORE THEIR POTENTIAL FOR TRANSLATION BY INDUSTRY AND CLINICAL HEPATOLOGISTS FOR THE DESIGN OF NOVEL THERAPEUTICS AND DIAGNOSTIC/PROGNOSTIC BIOMARKERS. IN PARTICULAR, WE PRESENT FINDINGS IN THE CONTEXT OF HEPATOCELLULAR CARCINOMA, FIBROSIS AND NON-ALCOHOLIC FATTY LIVER DISEASE, WHERE THERE IS URGENT UNMET NEED FOR NEW CLINICAL INTERVENTIONS AND BIOMARKERS. 2016 18 2322 24 EPIGENETIC REGULATION OF HEPATIC STELLATE CELL ACTIVATION AND LIVER FIBROSIS. CHRONIC LIVER INJURY TO HEPATOCYTES OR CHOLANGIOCYTES, WHEN LEFT UNMANAGED, LEADS TO THE DEVELOPMENT OF LIVER FIBROSIS, A CONDITION CHARACTERIZED BY THE EXCESSIVE INTRAHEPATIC DEPOSITION OF EXTRACELLULAR MATRIX PROTEINS. ACTIVATED HEPATIC STELLATE CELLS CONSTITUTE THE PREDOMINANT SOURCE OF EXTRACELLULAR MATRIX IN FIBROTIC LIVERS AND THEIR TRANSITION FROM A QUIESCENT STATE DURING FIBROGENESIS IS ASSOCIATED WITH IMPORTANT ALTERATIONS IN THEIR TRANSCRIPTIONAL AND EPIGENETIC LANDSCAPE. AREAS COVERED: WE BRIEFLY DESCRIBE THE PROCESSES INVOLVED IN HEPATIC STELLATE CELL ACTIVATION AND DISCUSS OUR CURRENT UNDERSTANDING OF ALTERATIONS IN THE EPIGENETIC LANDSCAPE, I.E DNA METHYLATION, HISTONE MODIFICATIONS AND THE FUNCTIONAL ROLE OF NON-CODING RNAS THAT ACCOMPANY THIS KEY EVENT IN THE DEVELOPMENT OF CHRONIC LIVER DISEASE. EXPERT COMMENTARY: ALTHOUGH GREAT PROGRESS HAS BEEN MADE, OUR UNDERSTANDING OF THE EPIGENETIC REGULATION OF HEPATIC STELLATE CELL ACTIVATION IS LIMITED AND, THUS FAR, INSUFFICIENT TO ALLOW THE DEVELOPMENT OF EPIGENETIC DRUGS THAT CAN SELECTIVELY INTERRUPT LIVER FIBROSIS. 2016 19 6882 16 [RESEARCH PROGRESS ON NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA]. PRIMARY LIVER CANCER ARISES FROM CHRONIC LIVER DISEASE, AND CIRRHOTIC LIVER GRADUALLY DEVELOPS INTO DYSPLASTIC NODULES THAT EVENTUALLY FORM MALIGNANT TUMORS. IN RECENT YEARS, MOLECULAR BIOTECHNOLOGY DEVELOPMENT HAS DEEPENED PEOPLE'S UNDERSTANDING ON THE PATHOGENESIS OF LIVER CANCER. EPIGENETIC MODIFICATIONS PLAY A SIGNIFICANT ROLE IN DNA METHYLATION, NON-CODING RNAS, CHROMATIN REMODELING, AND HISTONE MODIFICATION. THIS REVIEW FOCUSES ON THE PROGRESS OF CURRENTLY IMPLICATED NON-CODING RNAS IN THE MOLECULAR PATHOGENESIS OF HEPATOCELLULAR CARCINOMA, AND ITS POTENTIAL APPLICATION IN IMPROVING THE DIAGNOSIS AND TREATMENT. 2018 20 3932 22 LIVER REGENERATION, LIVER CANCERS AND CYCLINS. ACCUMULATING EVIDENCE HAS REVEALED THAT MALIGNANT CELL GROWTH IS REGULATED BY COMPLEX MECHANISMS INVOLVED IN GENETIC AND EPIGENETIC FACTORS. AMONG HUMAN CANCERS, CANCER IN THE LIVER (HEPATOCELLULAR CARCINOMA (HCC)) IS CHARACTERIZED BY THE EVIDENCE THAT IT IS USUALLY BASED ON CHRONIC LIVER DISEASES SUCH AS LIVER CIRRHOSIS OR CHRONIC HEPATITIS, IN WHICH THE LIVER IS PERSISTENTLY REGENERATING FOLLOWING HEPATIC INJURY. THIS RAISES THE POSSIBILITY THAT REPEATED HEPATOCYTE PROLIFERATION MAY CAUSE DISORDER OF GENES THAT ARE REGULATING THE CELL CYCLE IN HEPATOCYTES, THUS CAUSING HCC. IN THIS ARTICLE, RECENT STUDIES FOCUSING ON LIVER REGENERATION AND CANCER ARE REVIEWED FROM THE VIEWPOINT OF THE CELL CYCLE THAT IS REGULATED BY CYCLIN AND THE ASSOCIATED PROTEINS. 1998