1 3000 119 GENETIC VARIATIONS IN UCA1, A LNCRNA FUNCTIONING AS A MIRNA SPONGE, DETERMINE ENDOMETRIOSIS DEVELOPMENT AND THE POTENTIAL ASSOCIATED INFERTILITY VIA REGULATING LIPOGENESIS. ENDOMETRIOSIS IS A HORMONE-ASSOCIATED DISEASE WHICH HAS BEEN CONSIDERED AS THE PRECURSOR FOR CERTAIN TYPES OF OVARIAN CANCER. IN RECENT YEARS, EMERGING EVIDENCE DEMONSTRATED POTENT ROLES OF LNCRNA IN REGULATING CANCER DEVELOPMENT. SINCE ENDOMETRIOSIS SHARES SEVERAL FEATURES WITH CANCER, WE INVESTIGATED THE POSSIBLE INVOLVEMENT OF CANCER-RELATED LNCRNAS IN ENDOMETRIOSIS, INCLUDING UCA1, GAS5 AND PTENP1. BY USING MASSARRAY SYSTEM, WE INVESTIGATED CERTAIN GENETIC VARIATIONS IN CANCER-RELATED LNCRNAS THAT CAN CHANGE THE THERMO-STABILITY, LEADING TO UP-REGULATION OR DOWN-REGULATION OF THOSE LNCRNAS. OUR DATA INDICATED THREE RISK GENETIC HAPLOTYPES IN UCA1 WHICH CAN STABILIZE THE RNA STRUCTURE AND INCREASE THE SUSCEPTIBILITY OF ENDOMETRIOSIS. OF NOTE, SUCH ALTERATIONS WERE FOUND TO BE ASSOCIATED WITH LONG-TERM PAIN AND INFERTILITY IN PATIENTS. IT HAS BEEN KNOWN THAT UCA1 CAN FUNCTION AS A CERNA TO SPONGE AND INHIBIT MIRNAS, RESULTING IN LOSS-OF-CONTROL ON DOWNSTREAM TARGET GENES. GENE NETWORK ANALYSES REVEALED FATTY ACID METABOLISM AND MITOCHONDRIA BETA-OXIDATION AS THE MAJOR PATHWAYS ASSOCIATED WITH ALTERED UCA1 EXPRESSION IN ENDOMETRIOSIS PATIENTS. OUR STUDY THUS PROVIDES EVIDENCE TO HIGHLIGHT FUNCTIONAL/EPIGENETIC ROLES OF UCA1 IN ENDOMETRIOSIS DEVELOPMENT VIA REGULATING FATTY ACID METABOLISM IN WOMEN. 2022 2 1131 34 COMPREHENSIVE CIRCULAR RNA EXPRESSION PROFILING WITH ASSOCIATED CERNA NETWORK REVEALS THEIR THERAPEUTIC POTENTIAL IN CHOLESTEATOMA. CHOLESTEATOMA IS A CHRONIC DISEASE THAT PATHOLOGICALLY DISPLAYS A BENIGN TUMOR WITH EXCESSIVE SQUAMOUS EPITHELIAL CELL PROLIFERATION IN THE MIDDLE EAR. CLINICALLY, HOWEVER, IT CAN MANIFEST MALIGNANT BEHAVIOR BY DESTROYING ADJACENT TISSUES AND ORGANS. ALTHOUGH PREVIOUS STUDIES HAVE DEMONSTRATED THAT THE PATHOGENESIS OF CHOLESTEATOMA IS CORRELATED WITH EPIGENETIC DYSREGULATION, THE EXACT MECHANISM REMAINS UNCLEAR. CIRCULAR RNAS (CIRCRNAS) HAVE BEEN REVEALED AS BEING ABUNDANTLY EXPRESSED IN VARIOUS ORGANISMS AND HAVE BEEN FOUND TO CONTRIBUTE TO THE REGULATION OF MANY DISEASES. TO DATE, NO REPORTS HAVE ELUCIDATED THEIR EXPRESSION PROFILES AND FUNCTIONS IN CHOLESTEATOMA. IN THE PRESENT STUDY, THE CIRCRNA EXPRESSION PROFILE IN CHOLESTEATOMA WAS EXPLORED FOR THE FIRST TIME BY USING MICROARRAY ANALYSIS. WE OBTAINED A TOTAL OF 355 SIGNIFICANTLY DIFFERENTIALLY EXPRESSED CIRCRNAS IN CHOLESTEATOMA, AMONG WHICH 101 WERE IDENTIFIED TO BE UPREGULATED AND 254 DOWNREGULATED. BY CONSTRUCTING CIRCRNA?LNCRNA?MIRNA?MRNA COMPETING ENDOGENOUS RNA (CERNA) NETWORK, IT WAS DISCOVERED THAT CIRCRNAS MAY FUNCTION AS CERNAS AND CONTRIBUTE TO THE FORMATION OF CHOLESTEATOMA. THESE RESULTS PROVIDE NOVEL INSIGHT INTO THE PATHOGENESIS OF CHOLESTEATOMA AND SUGGEST CIRCRNAS AS POTENTIAL PROMISING THERAPEUTIC TARGETS FOR CHOLESTEATOMA. 2020 3 2876 32 FUNCTIONAL ROLES OF LONG NONCODING RNA MALAT1 IN GYNECOLOGIC CANCERS. GYNECOLOGIC CANCERS ARE REPRODUCTIVE DISORDERS CHARACTERIZED BY PELVIC PAIN AND INFERTILITY. THE IDENTIFICATION OF NEW PREDICTIVE MARKERS AND THERAPEUTIC TARGETS FOR THE TREATMENT OF GYNECOLOGIC CANCERS IS URGENTLY NECESSARY. ONE OF THE RECENT SUCCESSES IN GYNECOLOGIC CANCERS RESEARCH IS IDENTIFYING THE ROLE OF SIGNALING PATHWAYS IN THE PATHOGENESIS OF THE DISEASE. RECENT EXPERIMENTS SHOWED LONG NONCODING RNAS (LNCRNA) CAN BE NOVEL THERAPEUTIC APPROACHES FOR THE DIAGNOSIS AND TREATMENT OF GYNECOLOGIC CANCERS. LNCRNA ARE TRANSCRIBED RNA MOLECULES THAT PLAY PIVOTAL ROLES IN MULTIPLE BIOLOGICAL PROCESSES BY REGULATING THE DIFFERENT STEPS OF GENE EXPRESSION. METASTASIS-ASSOCIATED LUNG ADENOCARCINOMA TRANSCRIPT-1 (MALAT1) IS A WELL-KNOWN LNCRNA THAT PLAYS FUNCTIONAL ROLES IN GENE EXPRESSION, RNA PROCESSING, AND EPIGENETIC REGULATION. HIGH EXPRESSION OF MALAT1 IS CLOSELY RELATED TO NUMEROUS HUMAN DISEASES. IT IS GENERALLY BELIEVED THAT MALAT1 EXPRESSION IS ASSOCIATED WITH CANCER CELL GROWTH, AUTOPHAGY, INVASION, AND METASTASIS. MALAT1 BY TARGETING MULTIPLE SIGNALING PATHWAYS AND MICRORNAS (MIRNAS) COULD CONTRIBUTE TO THE PATHOGENESIS OF GYNECOLOGIC CANCERS. IN THIS REVIEW, WE WILL SUMMARIZE FUNCTIONAL ROLES OF MALAT1 IN THE MOST COMMON GYNECOLOGIC CANCERS, INCLUDING ENDOMETRIUM, BREAST, OVARY, AND CERVIX. 2023 4 2086 29 EPIGENETIC DYSREGULATION IN ENDOMETRIOSIS: IMPLICATIONS FOR PATHOPHYSIOLOGY AND THERAPEUTICS. ENDOMETRIOSIS IS A PREVALENT GYNECOLOGICAL CONDITION ASSOCIATED WITH PELVIC PAIN AND INFERTILITY. DESPITE MORE THAN A CENTURY OF RESEARCH, THE ETIOLOGY OF ENDOMETRIOSIS STILL ELUDES SCIENTIFIC CONSENSUS. THIS LACK OF CLARITY HAS RESULTED IN SUBOPTIMAL PREVENTION, DIAGNOSIS, AND TREATMENT OPTIONS. EVIDENCE OF GENETIC CONTRIBUTORS TO ENDOMETRIOSIS IS INTERESTING BUT LIMITED; HOWEVER, SIGNIFICANT PROGRESS HAS BEEN MADE IN RECENT YEARS IN IDENTIFYING EPIGENETIC ROLE IN THE PATHOGENESIS OF ENDOMETRIOSIS THROUGH CLINICAL STUDIES, IN VITRO CELL CULTURE EXPERIMENTS, AND IN VIVO ANIMAL MODELS. THE PREDOMINANT FINDINGS INCLUDE ENDOMETRIOSIS-RELATED DIFFERENTIAL EXPRESSION OF DNA METHYLTRANSFERASES AND DEMETHYLASES, HISTONE DEACETYLASES, METHYLTRANSFERASES, AND DEMETHYLASES, AND REGULATORS OF CHROMATIN ARCHITECTURE. THERE IS ALSO AN EMERGING ROLE FOR MIRNAS IN THE CONTROL OF EPIGENETIC REGULATORS IN THE ENDOMETRIUM AND ENDOMETRIOSIS. CHANGES IN THESE EPIGENETIC REGULATORS RESULT IN DIFFERENTIAL CHROMATIN ORGANIZATION AND DNA METHYLATION WITH CONSEQUENCES FOR GENE EXPRESSION INDEPENDENT OF A GENETIC SEQUENCE. EPIGENETICALLY ALTERED EXPRESSION OF GENES RELATED TO STEROID HORMONE PRODUCTION AND SIGNALING, IMMUNE REGULATION, AND ENDOMETRIAL CELL IDENTITY AND FUNCTION HAVE ALL BEEN IDENTIFIED AND APPEAR TO PLAY INTO THE PATHOPHYSIOLOGICAL MECHANISMS OF ENDOMETRIOSIS AS WELL AS RESULTING INFERTILITY. THIS REVIEW SUMMARIZES AND CRITICALLY DISCUSSES EARLY SEMINAL FINDINGS, THE EVER-GROWING RECENT EVIDENCE OF EPIGENETIC CONTRIBUTIONS TO THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS, AND IMPLICATIONS FOR PROPOSED EPIGENETICALLY TARGETED THERAPEUTICS. 2023 5 3005 31 GENETIC, EPIGENETIC, AND STEROIDOGENIC MODULATION MECHANISMS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE, AFFECTING UP TO 10% OF REPRODUCTIVE-AGE WOMEN. THE EXACT CAUSE OF THE DISEASE IS UNKNOWN; HOWEVER, IT IS A HERITABLE CONDITION AFFECTED BY MULTIPLE GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. PREVIOUS STUDIES REPORTED VARIATIONS IN THE EPIGENETIC PATTERNS OF NUMEROUS GENES KNOWN TO BE INVOLVED IN THE ABERRANT MODULATION OF CELL CYCLE STEROIDOGENESIS, ABNORMAL HORMONAL, IMMUNE AND INFLAMMATORY STATUS IN ENDOMETRIOSIS, APOPTOSIS, ADHESION, ANGIOGENESIS, PROLIFERATION, IMMUNE AND INFLAMMATORY PROCESSES, RESPONSE TO HYPOXIA, STEROIDOGENIC PATHWAY AND HORMONE SIGNALING ARE INVOLVED IN THE PATHOGENESIS OF ENDOMETRIOSIS. ACCUMULATING EVIDENCE SUGGEST THAT VARIOUS EPIGENETIC ABERRATIONS MAY CONTRIBUTE TO THE PATHOGENESIS OF ENDOMETRIOSIS. AMONG THEM, DNA METHYLTRANSFERASES, HISTONE DEACETYLATORS, AND NON-CODING MICRORNAS DEMONSTRATE DIFFERENTIAL EXPRESSION WITHIN ENDOMETRIOTIC LESIONS AND IN THE ENDOMETRIUM OF PATIENTS WITH ENDOMETRIOSIS. IT HAS BEEN INDICATED THAT THE IDENTIFICATION OF EPIGENETIC DIFFERENCES WITHIN THE DNA OR HISTONE PROTEINS MAY CONTRIBUTE TO THE DISCOVERY OF A USEFUL PROGNOSTIC BIOMARKER, WHICH COULD AID IN THE FUTURE EARLIER DETECTION, TIMELY DIAGNOSIS, AND INITIATION OF A NEW APPROACH TO THE TREATMENT OF ENDOMETRIOSIS, AS WELL AS INFORM US ABOUT THE EFFECTIVENESS OF TREATMENT AND THE STAGE OF THE DISEASE. AS THE ETIOLOGY OF ENDOMETRIOSIS IS HIGHLY COMPLEX AND STILL FAR FROM BEING FULLY ELUCIDATED, THE PRESENTED REVIEW FOCUSES ON DIFFERENT APPROACHES TO IDENTIFY THE GENETIC AND EPIGENETIC LINKS OF ENDOMETRIOSIS AND ITS PATHOGENESIS. 2020 6 2909 35 GENE EXPRESSION PROFILING IN FIBROMYALGIA INDICATES AN AUTOIMMUNE ORIGIN OF THE DISEASE AND OPENS NEW AVENUES FOR TARGETED THERAPY. FIBROMYALGIA IS A CHRONIC DISORDER CHARACTERIZED BY WIDESPREAD PAIN AND BY SEVERAL NON-PAIN SYMPTOMS. AUTOIMMUNITY, SMALL FIBER NEUROPATHY AND NEUROINFLAMMATION HAVE BEEN SUGGESTED TO BE INVOLVED IN THE PATHOGENESIS OF THE DISEASE. WE HAVE INVESTIGATED THE GENE EXPRESSION PROFILE IN PERIPHERAL BLOOD MONONUCLEAR CELLS OBTAINED FROM TEN PATIENTS AND TEN HEALTHY SUBJECTS. OF THE 545,500 TRANSCRIPTS ANALYZED, 1673 RESULTED MODULATED IN FIBROMYALGIC PATIENTS. THE MAJORITY OF THESE GENES ARE INVOLVED IN BIOLOGICAL PROCESSES AND PATHWAYS LINKED TO THE CLINICAL MANIFESTATIONS OF THE DISEASE. MOREOVER, GENES INVOLVED IN IMMUNOLOGICAL PATHWAYS CONNECTED TO INTERLEUKIN-17 AND TO TYPE I INTERFERON SIGNATURES WERE ALSO MODULATED, SUGGESTING THAT AUTOIMMUNITY PLAYS A ROLE IN THE DISEASE. WE THEN AIMED AT IDENTIFYING DIFFERENTIALLY EXPRESSED LONG NON-CODING RNAS (LNCRNAS) FUNCTIONALLY CONNECTED TO MODULATED GENES BOTH DIRECTLY AND VIA MICRORNA TARGETING. ONLY TWO LNCRNAS OF THE 298 FOUND MODULATED IN PATIENTS, WERE ABLE TO TARGET THE MOST HIGHLY CONNECTED GENES IN THE FIBROMYALGIA INTERACTOME, SUGGESTING THEIR INVOLVEMENT IN CRUCIAL GENE REGULATION. OUR GENE EXPRESSION DATA WERE CONFIRMED BY REAL TIME PCR, BY AUTOANTIBODY TESTING, DETECTION OF SOLUBLE MEDIATORS AND TH-17 POLARIZATION IN A VALIDATION COHORT OF 50 PATIENTS. OUR RESULTS INDICATE THAT GENETIC AND EPIGENETIC MECHANISMS AS WELL AS AUTOIMMUNITY PLAY A PIVOTAL ROLE IN THE PATHOGENESIS OF FIBROMYALGIA. 2020 7 4285 35 MICRORNA EPIGENETIC SIGNATURES IN HUMAN DISEASE. MICRORNAS (MIRNAS) ARE SHORT NON-CODING RNAS THAT ACT AS IMPORTANT REGULATORS OF GENE EXPRESSION AS PART OF THE EPIGENETIC MACHINERY. IN ADDITION TO POSTTRANSCRIPTIONAL GENE SILENCING BY MIRNAS, THE EPIGENETIC MECHANISMS ALSO INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND THEIR CROSSTALK. EPIGENETIC MODIFICATIONS WERE REPORTED TO PLAY AN IMPORTANT ROLE IN MANY DISEASE ONSETS AND PROGRESSIONS AND CAN BE USED TO EXPLAIN SEVERAL FEATURES OF COMPLEX DISEASES, SUCH AS LATE ONSET AND FLUCTUATION OF SYMPTOMS. HOWEVER, MIRNAS NOT ONLY FUNCTION AS A PART OF EPIGENETIC MACHINERY, BUT ARE ALSO EPIGENETICALLY MODIFIED BY DNA METHYLATION AND HISTONE MODIFICATION LIKE ANY OTHER PROTEIN-CODING GENE. THERE IS A STRONG CONNECTION BETWEEN EPIGENOME AND MIRNOME, AND ANY DYSREGULATION OF THIS COMPLEX SYSTEM CAN RESULT IN VARIOUS PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS. IN ADDITION, MIRNAS PLAY AN IMPORTANT ROLE IN TOXICOGENOMICS AND MAY EXPLAIN THE RELATIONSHIP BETWEEN TOXICANT EXPOSURE AND TUMORIGENESIS. THE PRESENT REVIEW PROVIDES INFORMATION ON 63 MIRNA GENES SHOWN TO BE EPIGENETICALLY REGULATED IN ASSOCIATION WITH 21 DISEASES, INCLUDING 11 CANCER TYPES: CARDIAC FIBROSIS, CARDIOVASCULAR DISEASE, PREECLAMPSIA, HIRSCHSPRUNG'S DISEASE, RHEUMATOID ARTHRITIS, SYSTEMIC SCLEROSIS, SYSTEMIC LUPUS ERYTHEMATOSUS, TEMPORAL LOBE EPILEPSY, AUTISM, PULMONARY FIBROSIS, MELANOMA, ACUTE MYELOID LEUKEMIA, CHRONIC LYMPHOCYTIC LEUKEMIA, COLORECTAL, GASTRIC, CERVICAL, OVARIAN, PROSTATE, LUNG, BREAST, AND BLADDER CANCER. THE REVIEW REVEALED THAT HSA-MIR-34A, HSA-MIR-34B, AND HSA-MIR-34C ARE THE MOST FREQUENTLY REPORTED EPIGENETICALLY DYSREGULATED MIRNAS. THERE IS A NEED TO FURTHER STUDY MOLECULAR MECHANISMS OF VARIOUS DISEASES TO BETTER UNDERSTAND THE CROSSTALK BETWEEN EPIGENETICS AND GENE EXPRESSION AND TO DEVELOP NEW THERAPEUTIC OPTIONS AND BIOMARKERS. 2016 8 3003 38 GENETIC, EPIGENETIC AND STEM CELL ALTERATIONS IN ENDOMETRIOSIS: NEW INSIGHTS AND POTENTIAL THERAPEUTIC PERSPECTIVES. HUMAN ENDOMETRIUM IS A HIGHLY DYNAMIC TISSUE, UNDERGOING PERIODIC GROWTH AND REGRESSION AT EACH MENSTRUAL CYCLE. ENDOMETRIOSIS IS A FREQUENT CHRONIC PATHOLOGICAL STATUS CHARACTERIZED BY ENDOMETRIAL TISSUE WITH AN ECTOPIC LOCALIZATION, CAUSING PELVIC PAIN AND INFERTILITY AND A VARIABLE CLINICAL PRESENTATION. IN ADDITION, THERE IS WELL-ESTABLISHED EVIDENCE THAT, ALTHOUGH ENDOMETRIOSIS IS CONSIDERED BENIGN, IT IS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT TRANSFORMATION IN APPROXIMATELY 1.0% OF AFFECTED WOMEN, WITH THE INVOLVEMENT OF MULTIPLE PATHWAYS OF DEVELOPMENT. INCREASING EVIDENCE SUPPORTS A KEY CONTRIBUTION OF DIFFERENT STEM/PROGENITOR CELL POPULATIONS NOT ONLY IN THE CYCLIC REGENERATION OF EUTOPIC ENDOMETRIUM, BUT ALSO IN THE PATHOGENESIS OF AT LEAST SOME TYPES OF ENDOMETRIOSIS. EVIDENCE HAS ARISEN FROM EXPERIMENTS IN ANIMAL MODELS OF DISEASE THROUGH DIFFERENT KINDS OF ASSAYS (INCLUDING CLONOGENICITY, THE LABEL-RETAINING CELL APPROACH, THE ANALYSIS OF UNDIFFERENTIATION MARKERS), AS WELL AS FROM DESCRIPTIVE STUDIES ON ECTOPIC AND EUTOPIC TISSUE SAMPLES HARVESTED FROM AFFECTED WOMEN. CHANGES IN STEM CELL POPULATIONS IN ENDOMETRIOTIC LESIONS ARE ASSOCIATED WITH GENETIC AND EPIGENETIC ALTERATIONS, INCLUDING IMBALANCE OF MIRNA EXPRESSION, HISTONE AND DNA MODIFICATIONS AND CHROMOSOMAL ABERRATIONS. THE PRESENT SHORT REVIEW MAINLY SUMMARIZES THE LATEST OBSERVATIONS CONTRIBUTING TO THE CURRENT KNOWLEDGE REGARDING THE PRESENCE AND THE POTENTIAL CONTRIBUTION OF STEM/PROGENITOR CELLS IN EUTOPIC ENDOMETRIUM AND THE AETIOLOGY OF ENDOMETRIOSIS, TOGETHER WITH A REPORT OF THE MOST RECENTLY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS IN ENDOMETRIOSIS. WE ALSO DESCRIBE THE POTENTIAL ADVANTAGES OF SINGLE CELL MOLECULAR PROFILING IN ENDOMETRIUM AND IN ENDOMETRIOTIC LESIONS. ALL THESE DATA CAN HAVE CLINICAL IMPLICATIONS AND PROVIDE A BASIS FOR NEW POTENTIAL THERAPEUTIC APPLICATIONS. 2014 9 4289 32 MICRORNA IN OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT DEGENERATIVE JOINT DISEASE AND IS ACCOMPANIED BY PAIN AND JOINT DYSFUNCTION. ITS CLINICAL TREATMENT TENDS TO BE UNSATISFACTORY. NOVEL TARGETS IN OA INCLUDE GENES THAT ARE INVOLVED IN OA PATHOPHYSIOLOGY AND HAVE BEEN DISCOVERED USING GENE NETWORK, EPIGENETIC AND MICRORNA (MIRNA) APPROACHES. MIRNA HAS BEEN IMPLICATED IN IMPORTANT CELLULAR PROCESSES SUCH AS LIPID METABOLISM, APOPTOSIS, DIFFERENTIATION AND ORGAN DEVELOPMENT. THE IMPORTANCE OF MIRNA REGULATION IN CELLULAR FUNCTION IS BECOMING INCREASINGLY CLEAR AS NEW MIRNA TARGETS ARE REVEALED. THE PRESENT REVIEW SUMMARIZES THE CURRENT EVIDENCE OF THE IMPORTANT ROLE PLAYED BY MIRNA IN DETERMINING THE COMPLEX GENE EXPRESSION PATTERNS OF OA CHONDROCYTES AND THEIR ROLE IN THE REGULATION OF TRANSCRIPTION, AND POSSIBLE DEMETHYLATION MECHANISMS THAT MIGHT BE APPLICABLE IN OA. IN SUMMARY, MIRNA MAY HAVE IMPORTANT DIAGNOSTIC AND THERAPEUTIC POTENTIAL, AND MIGHT PROVIDE A NOVEL MEANS OF TREATING OA. 2011 10 1028 30 CIRCULATING MIRNAS RELATED TO EPITHELIAL-MESENCHYMAL TRANSITIONS (EMT) AS THE NEW MOLECULAR MARKERS IN ENDOMETRIOSIS. ENDOMETRIOSIS IS A CHRONIC GYNECOLOGICAL DISEASE DEFINED BY THE PRESENCE OF ENDOMETRIAL-LIKE TISSUE FOUND OUTSIDE THE UTERUS, MOST COMMONLY IN THE PERITONEAL CAVITY. ENDOMETRIOSIS LESIONS ARE HETEROGENOUS BUT USUALLY CONTAIN ENDOMETRIAL STROMAL CELLS AND EPITHELIAL GLANDS, IMMUNE CELL INFILTRATES AND ARE VASCULARIZED AND INNERVATED BY NERVES. THE COMPLEX ETIOPATHOGENESIS AND HETEROGENITY OF THE CLINICAL SYMPTOMS, AS WELL AS THE LACK OF A SPECIFIC NON-INVASIVE DIAGNOSTIC BIOMARKERS, UNDERLINE THE NEED FOR MORE ADVANCED DIAGNOSTIC TOOLS. UNFORTUNATELY, THE CONTRIBUTION OF ENVIRONMENTAL, HORMONAL AND IMMUNOLOGICAL FACTORS IN THE DISEASE ETIOLOGY IS INSUFFICIENT, AND THE CONTRIBUTION OF GENETIC/EPIGENETIC FACTORS IS STILL FRAGMENTARY. THEREFORE, THERE IS A NEED FOR MORE FOCUSED STUDY ON THE MOLECULAR MECHANISMS OF ENDOMETRIOSIS AND NON-INVASIVE DIAGNOSTIC MONITORING SYSTEMS. MICRORNAS (MIRNAS) DEMONSTRATE HIGH STABILITY AND TISSUE SPECIFICITY AND PLAY A SIGNIFICANT ROLE IN MODULATING A RANGE OF MOLECULAR PATHWAYS, AND HENCE MAY BE SUITABLE DIAGNOSTIC BIOMARKERS FOR THE ORIGIN AND DEVELOPMENT OF ENDOMETRIOSIS. OF THESE, THE MOST FREQUENTLY STUDIED ARE THOSE RELATED TO ENDOMETRIOSIS, INCLUDING THOSE INVOLVED IN EPITHELIAL-MESENCHYMAL TRANSITION (EMT), WHOSE EXPRESSION IS ALTERED IN PLASMA OR ENDOMETRIOTIC LESION BIOPSIES; HOWEVER, THE RESULTS ARE AMBIGUOUS. SPECIFIC MIRNAS EXPRESSED IN ENDOMETRIOSIS MAY SERVE AS DIAGNOSTICS MARKERS WITH PROGNOSTIC VALUE, AND THEY HAVE BEEN PROPOSED AS MOLECULAR TARGETS FOR TREATMENT. THE AIM OF THIS REVIEW IS TO PRESENT SELECTED MIRNAS ASSOCIATED WITH EMT KNOWN TO HAVE EXPERIMENTALLY CONFIRMED SIGNIFICANCE, AND DISCUSS THEIR UTILITY AS BIOMARKERS IN ENDOMETRIOSIS. 2021 11 4228 19 METHYLATION OF INFLAMMATORY CELLS IN LUNG DISEASES. THIS CHAPTER OVERVIEWS ROLES OF DNA METHYLATION IN INFLAMMATORY CELL BIOLOGY WITH THE FOCUSES ON LYMPHOCYTES AND MACROPHAGES/MONOCYTES IN LUNG DISEASES, ALTHOUGH THE MOLECULAR MECHANISMS BY WHICH TARGET GENES ARE METHYLATED AND REGULATED IN LUNG DISEASES REMAIN UNCLEAR. MOST OF EPIGENETIC STUDIES ON DNA METHYLATION OF TARGET GENES IN LUNG DISEASES MAINLY DEMONSTRATED THE CORRELATION OF DNA METHYLATION OF TARGET GENES WITH THE LEVELS OF OTHER CORRESPONDING FACTORS, WITH THE SPECIFICITY OF CLINICAL PHENOMES, AND WITH THE SEVERITY OF LUNG DISEASES. THERE IS AN URGENT NEED TO IDENTIFY AND VALIDATE THE SPECIFICITY AND REGULATORY MECHANISMS OF INFLAMMATORY CELL EPIGENETICS IN DEPTH. THE EPIGENETIC HETEROGENEITY AMONG DIFFERENT SUBSETS OF T CELLS AND AMONG PROMOTERS OR NON-PROMOTERS OF TARGET GENES SHOULD BE FURTHERMORE CLARIFIED IN ACUTE OR CHRONIC LUNG DISEASES AND CANCERS. THE HYPER/HYPO-METHYLATION AND MODIFICATIONS OF CHROMOSOL AND EXTRACHROMOSOMAL DNA MAY RESULT IN ALTERNATIONS IN PROTEINS WITHIN INFLAMMATORY CELLS, WHICH CAN BE IDENTIFIED AS DISEASE-SPECIFIC BIOMARKERS AND THERAPEUTIC TARGETS. 2020 12 6340 25 THE ROLE OF EPIGENETIC FACTORS IN PSORIASIS. PSORIASIS IS A CHRONIC, SYSTEMIC, IMMUNE-MEDIATED DISEASE WITH AN INCIDENCE OF APPROXIMATELY 2%. THE PATHOGENESIS OF THE DISEASE IS COMPLEX AND NOT YET FULLY UNDERSTOOD. GENETIC FACTORS PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF THE DISEASE. IN PREDISPOSED INDIVIDUALS, MULTIPLE TRIGGER FACTORS MAY CONTRIBUTE TO DISEASE ONSET AND EXACERBATIONS OF SYMPTOMS. ENVIRONMENTAL FACTORS (STRESS, INFECTIONS, CERTAIN MEDICATIONS, NICOTINISM, ALCOHOL, OBESITY) PLAY A SIGNIFICANT ROLE IN THE PATHOGENESIS OF PSORIASIS. IN ADDITION, EPIGENETIC MECHANISMS ARE CONSIDERED RESULT IN MODULATION OF INDIVIDUAL GENE EXPRESSION AND AN INCREASED LIKELIHOOD OF THE DISEASE. STUDIES HIGHLIGHT THE SIGNIFICANT ROLE OF EPIGENETIC FACTORS IN THE ETIOLOGY AND PATHOGENESIS OF PSORIASIS. EPIGENETIC MECHANISMS IN PSORIASIS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND NON-CODING RNAS. EPIGENETIC MECHANISMS INDUCE GENE EXPRESSION CHANGES UNDER THE INFLUENCE OF CHEMICAL MODIFICATIONS OF DNA AND HISTONES, WHICH ALTER CHROMATIN STRUCTURE AND ACTIVATE TRANSCRIPTION FACTORS OF SELECTED GENES, THUS LEADING TO TRANSLATION OF NEW MRNA WITHOUT AFFECTING THE DNA SEQUENCE. EPIGENETIC FACTORS CAN REGULATE GENE EXPRESSION AT THE TRANSCRIPTIONAL (VIA HISTONE MODIFICATION, DNA METHYLATION) AND POSTTRANSCRIPTIONAL LEVELS (VIA MICRORNAS AND LONG NON-CODING RNAS). THIS STUDY AIMS TO PRESENT AND DISCUSS THE DIFFERENT EPIGENETIC MECHANISMS IN PSORIASIS BASED ON A REVIEW OF THE AVAILABLE LITERATURE. 2021 13 3961 32 LONG NON-CODING RNAS: THE NEW FRONTIER INTO UNDERSTANDING THE ETIOLOGY OF ALCOHOL USE DISORDER. ALCOHOL USE DISORDER (AUD) IS A COMPLEX, CHRONIC, DEBILITATING CONDITION IMPACTING MILLIONS WORLDWIDE. GENETIC, ENVIRONMENTAL, AND EPIGENETIC FACTORS ARE KNOWN TO CONTRIBUTE TO THE DEVELOPMENT OF AUD. LONG NON-CODING RNAS (LNCRNAS) ARE A CLASS OF REGULATORY RNAS, COMMONLY REFERRED TO AS THE "DARK MATTER" OF THE GENOME, WITH LITTLE TO NO PROTEIN-CODING POTENTIAL. LNCRNAS HAVE BEEN IMPLICATED IN NUMEROUS PROCESSES CRITICAL FOR CELL SURVIVAL, SUGGESTING THAT THEY PLAY IMPORTANT FUNCTIONAL ROLES IN REGULATING DIFFERENT CELL PROCESSES. LNCRNAS WERE ALSO SHOWN TO DISPLAY HIGHER TISSUE SPECIFICITY THAN PROTEIN-CODING GENES AND HAVE A HIGHER ABUNDANCE IN THE BRAIN AND CENTRAL NERVOUS SYSTEM, DEMONSTRATING A POSSIBLE ROLE IN THE ETIOLOGY OF PSYCHIATRIC DISORDERS. INDEED, GENETIC (E.G., GENOME-WIDE ASSOCIATION STUDIES (GWAS)), MOLECULAR (E.G., EXPRESSION QUANTITATIVE TRAIT LOCI (EQTL)) AND EPIGENETIC STUDIES FROM POSTMORTEM BRAIN TISSUES HAVE IDENTIFIED A GROWING LIST OF LNCRNAS ASSOCIATED WITH NEUROPSYCHIATRIC AND SUBSTANCE USE DISORDERS. GIVEN THAT THE EXPRESSION PATTERNS OF LNCRNAS HAVE BEEN ASSOCIATED WITH WIDESPREAD CHANGES IN THE TRANSCRIPTOME, INCLUDING METHYLATION, CHROMATIN ARCHITECTURE, AND ACTIVATION OR SUPPRESSION OF TRANSLATIONAL ACTIVITY, THE REGULATORY NATURE OF LNCRNAS MAY BE UBIQUITOUS AND AN INNATE COMPONENT OF GENE REGULATION. IN THIS REVIEW, WE PRESENT A SYNOPSIS OF THE FUNCTIONAL IMPACT THAT LNCRNAS MAY PLAY IN THE ETIOLOGY OF AUD. WE ALSO DISCUSS THE CLASSIFICATIONS OF LNCRNAS, THEIR KNOWN FUNCTIONAL ROLES, AND THERAPEUTIC ADVANCEMENTS IN THE FIELD OF LNCRNAS TO FURTHER CLARIFY THE FUNCTIONAL RELATIONSHIP BETWEEN LNCRNAS AND AUD. 2022 14 3503 28 IDENTIFICATION OF POTENTIAL DIFFERENTIALLY METHYLATED GENE-RELATED BIOMARKERS IN ENDOMETRIOSIS. AIM: TO IDENTIFY EPIGENETIC ALTERATIONS OF DIFFERENTIALLY EXPRESSED GENES AND SCREEN OUT TARGETED THERAPEUTIC DRUGS IN ENDOMETRIOSIS. METHODS: BASED ON THE GENE EXPRESSION OMNIBUS DATABASE AND A SERIES OF BIOLOGICAL INFORMATION ANALYSIS TOOLS, SUPPLEMENTED BY VALIDATION OF CLINICAL SAMPLES, ABERRANT DNA METHYLATION-DRIVEN GENES AND THEIR FUNCTIONS WERE EXPLORED, AS WELL AS POSSIBLE TARGETED DRUGS. RESULTS: THIS STUDY SCREENED OUT A RANGE OF DNA METHYLATION-DRIVEN GENES THAT WERE ASSOCIATED WITH POWERFUL PROPERTIES AND CORRESPONDING PATHWAYS. AMONG THEM, BDNF AND CCL2 WERE KEY GENES IN THE DEVELOPMENT OF ENDOMETRIOSIS. FOUR CHEMICAL AGENTS HAVE BEEN FLAGGED AS POTENTIAL TREATMENTS FOR ENDOMETRIOSIS. CONCLUSION: THESE CANDIDATE GENES AND SMALL-MOLECULE AGENTS MAY BE FURTHER EXPLORED AS POTENTIAL TARGETS AND DRUGS FOR ENDOMETRIOSIS DIAGNOSIS AND THERAPY, RESPECTIVELY. 2022 15 3772 25 INTERACTION BETWEEN MICRORNA AND DNA METHYLATION IN ATHEROSCLEROSIS. ATHEROSCLEROSIS (AS) IS A CHRONIC INFLAMMATORY DISEASE ACCOMPANIED BY COMPLEX PATHOLOGICAL CHANGES, SUCH AS ENDOTHELIAL DYSFUNCTION, FOAM CELL FORMATION, AND VASCULAR SMOOTH MUSCLE CELL PROLIFERATION. MANY APPROACHES, INCLUDING REGULATING AS-RELATED GENE EXPRESSION IN THE TRANSCRIPTIONAL OR POST-TRANSCRIPTIONAL LEVEL, CONTRIBUTE TO ALLEVIATING AS DEVELOPMENT. THE DNA METHYLATION IS A CRUCIAL EPIGENETIC MODIFICATION IN REGULATING CELL FUNCTION BY SILENCING THE RELATIVE GENE EXPRESSION. THE MICRORNA (MIRNA) IS A TYPE OF NONCODING RNA THAT PLAYS AN IMPORTANT ROLE IN GENE POST-TRANSCRIPTIONAL REGULATION AND DISEASE DEVELOPMENT. THE DNA METHYLATION AND THE MIRNA ARE IMPORTANT EPIGENETIC FACTORS IN AS. HOWEVER, RECENT STUDIES HAVE FOUND A MUTUAL REGULATION BETWEEN THESE TWO FACTORS IN AS DEVELOPMENT. IN THIS STUDY, RECENT INSIGHTS INTO THE ROLES OF MIRNA AND DNA METHYLATION AND THEIR INTERACTION IN THE AS PROGRESSION ARE REVIEWED. 2021 16 3960 33 LONG NON-CODING RNAS: A DOUBLE-EDGED SWORD IN AGING KIDNEY AND RENAL DISEASE. AGING AS ONE OF INTRINSIC BIOLOGICAL PROCESSES IS A RISK FACTOR FOR MANY CHRONIC DISEASES. KIDNEY DISEASE IS A GLOBAL PROBLEM AND HEALTH CARE BURDEN WORLDWIDE. THE DIAGNOSIS OF KIDNEY DISEASE IS CURRENTLY BASED ON SERUM CREATININE AND UREA LEVELS. NOVEL BIOMARKERS MAY IMPROVE DIAGNOSTIC ACCURACY, THEREBY ALLOWING EARLY PREVENTION AND TREATMENT. OVER THE PAST FEW YEARS, ADVANCES IN GENOME ANALYSES HAVE IDENTIFIED AN EMERGING CLASS OF NONCODING RNAS THAT PLAY CRITICAL ROLES IN THE REGULATION OF GENE EXPRESSION AND EPIGENETIC REPROGRAMMING. LONG NONCODING RNAS (LNCRNAS) ARE PERVASIVELY TRANSCRIBED IN THE GENOME AND COULD BIND DNA, RNA AND PROTEIN. EMERGING EVIDENCE HAS DEMONSTRATED THAT LNCRNAS PLAYED AN IMPORTANT ROLE IN ALL STAGES OF KIDNEY DISEASE. TO DATE, ONLY SOME LNCRNAS WERE WELL IDENTIFIED AND CHARACTERIZED, BUT THE COMPLEXITY OF MULTILEVEL REGULATION OF TRANSCRIPTIONAL PROGRAMS INVOLVED IN THESE PROCESSES REMAINS UNDEFINED. IN THIS REVIEW, WE SUMMARIZED THE LNCRNA EXPRESSION PROFILING OF LARGE-SCALE IDENTIFIED LNCRNAS ON KIDNEY DISEASES INCLUDING ACUTE KIDNEY INJURY, CHRONIC KIDNEY DISEASE, DIABETIC NEPHROPATHY AND KIDNEY TRANSPLANTATION. WE FURTHER DISCUSSED A NUMBER OF ANNOTATED LNCRNAS LINKING WITH COMPLEX ETIOLOGY OF KIDNEY DISEASES. FINALLY, SEVERAL LNCRNAS WERE HIGHLIGHTED AS DIAGNOSTIC BIOMARKERS AND THERAPEUTIC TARGETS. TARGETING LNCRNAS MAY REPRESENT A PRECISE THERAPEUTIC STRATEGY FOR PROGRESSIVE RENAL FIBROSIS. 2021 17 3834 31 INVOLVEMENTS OF LONG NONCODING RNAS IN OBESITY-ASSOCIATED INFLAMMATORY DISEASES. OBESITY IS ASSOCIATED WITH CHRONIC LOW-GRADE INFLAMMATION THAT AFFECTS THE PHENOTYPE OF MULTIPLE TISSUES AND THEREFORE IS IMPLICATED IN THE DEVELOPMENT AND PROGRESSION OF SEVERAL AGE-RELATED CHRONIC INFLAMMATORY DISORDERS. IMPORTANTLY, A NEW FAMILY OF NONCODING RNAS, TERMED LONG NONCODING RNAS (LNCRNAS), HAVE BEEN IDENTIFIED AS KEY REGULATORS OF INFLAMMATORY SIGNALLING PATHWAYS THAT CAN MEDIATE BOTH PRETRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL GENE REGULATION. FURTHERMORE, SEVERAL LNCRNAS HAVE BEEN IDENTIFIED, WHICH ARE DIFFERENTIALLY EXPRESSED IN MULTIPLE TISSUE TYPES IN INDIVIDUALS WHO ARE OBESE OR IN PRECLINICAL MODELS OF OBESITY. IN THIS REVIEW, WE EXAMINE THE EVIDENCE FOR THE ROLE OF SEVERAL OF THE MOST WELL-STUDIED LNCRNAS IN THE REGULATION OF INFLAMMATORY PATHWAYS ASSOCIATED WITH OBESITY. WE HIGHLIGHT THE EVIDENCE FOR THEIR DIFFERENTIAL EXPRESSION IN THE OBESE STATE AND IN AGE-RELATED CONDITIONS INCLUDING INSULIN RESISTANCE, TYPE 2 DIABETES (T2D), SARCOPENIA, OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS, WHERE OBESITY PLAYS A SIGNIFICANT ROLE. DETERMINING THE EXPRESSION AND FUNCTIONAL ROLE OF LNCRNAS IN MEDIATING OBESITY-ASSOCIATED CHRONIC INFLAMMATION WILL ADVANCE OUR UNDERSTANDING OF THE EPIGENETIC REGULATORY PATHWAYS THAT UNDERLIE AGE-RELATED INFLAMMATORY DISEASES AND MAY ALSO ULTIMATELY IDENTIFY NEW TARGETS FOR THERAPEUTIC INTERVENTION. 2021 18 5264 29 PROMISING DIRECTIONS IN ATHEROSCLEROSIS TREATMENT BASED ON EPIGENETIC REGULATION USING MICRORNAS AND LONG NONCODING RNAS. ATHEROSCLEROSIS IS ONE OF THE LEADING CAUSES OF MORTALITY FROM CARDIOVASCULAR DISEASE (CVD) AND IS A CHRONIC INFLAMMATORY DISEASE OF THE MIDDLE AND LARGE ARTERIES CAUSED BY A DISRUPTION OF LIPID METABOLISM. NONCODING RNA (NCRNA), INCLUDING MICRORNA (MIRNA), SMALL INTERFERING RNA (SIRNA) AND LONG NONCODING RNA (LNCRNA), WAS INVESTIGATED FOR THE TREATMENT OF ATHEROSCLEROSIS. REGULATION OF THE EXPRESSION OF NONCODING RNA TARGETS THE CONSTITUENT ELEMENT OF THE PATHOGENESIS OF ATHEROSCLEROSIS. CURRENTLY, MIRNA THERAPY COMMONLY EMPLOYS MIRNA ANTAGONISTS AND MIMIC COMPOUNDS. IN THIS REVIEW, ATTENTION IS FOCUSED ON APPROACHES TO CORRECTING MOLECULAR DISORDERS BASED ON THE GENETIC REGULATION OF THE TRANSCRIPTION OF KEY GENES RESPONSIBLE FOR THE DEVELOPMENT OF ATHEROSCLEROSIS. PROMISING TECHNOLOGIES WERE CONSIDERED FOR THE TREATMENT OF ATHEROSCLEROSIS, AND EXAMPLES ARE GIVEN FOR TECHNOLOGIES THAT HAVE BEEN SHOWN TO BE EFFECTIVE IN CLINICAL TRIALS. 2019 19 1020 26 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 20 2523 35 EPIGENETICS AND THE TRANSITION FROM ACUTE TO CHRONIC PAIN. OBJECTIVE: THE OBJECTIVE OF THIS STUDY WAS TO REVIEW THE EPIGENETIC MODIFICATIONS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN AND TO IDENTIFY POTENTIAL TARGETS FOR THE DEVELOPMENT OF NOVEL, INDIVIDUALIZED PAIN THERAPEUTICS. BACKGROUND: EPIGENETICS IS THE STUDY OF HERITABLE MODIFICATIONS IN GENE EXPRESSION AND PHENOTYPE THAT DO NOT REQUIRE A CHANGE IN GENETIC SEQUENCE TO MANIFEST THEIR EFFECTS. ENVIRONMENTAL TOXINS, MEDICATIONS, DIET, AND PSYCHOLOGICAL STRESSES CAN ALTER EPIGENETIC PROCESSES SUCH AS DNA METHYLATION, HISTONE ACETYLATION, AND RNA INTERFERENCE. AS EPIGENETIC MODIFICATIONS POTENTIALLY PLAY AN IMPORTANT ROLE IN INFLAMMATORY CYTOKINE METABOLISM, STEROID RESPONSIVENESS, AND OPIOID SENSITIVITY, THEY ARE LIKELY KEY FACTORS IN THE DEVELOPMENT OF CHRONIC PAIN. ALTHOUGH OUR KNOWLEDGE OF THE HUMAN GENETIC CODE AND DISEASE-ASSOCIATED POLYMORPHISMS HAS GROWN SIGNIFICANTLY IN THE PAST DECADE, WE HAVE NOT YET BEEN ABLE TO ELUCIDATE THE MECHANISMS THAT LEAD TO THE DEVELOPMENT OF PERSISTENT PAIN AFTER NERVE INJURY OR SURGERY. DESIGN: THIS IS A FOCUSED LITERATURE REVIEW OF EPIGENETIC SCIENCE AND ITS RELATIONSHIP TO CHRONIC PAIN. RESULTS: SIGNIFICANT LABORATORY AND CLINICAL DATA SUPPORT THE NOTION THAT EPIGENETIC MODIFICATIONS ARE AFFECTED BY THE ENVIRONMENT AND LEAD TO DIFFERENTIAL GENE EXPRESSION. SIMILAR TO MECHANISMS INVOLVED IN THE DEVELOPMENT OF CANCER, NEURODEGENERATIVE DISEASE, AND INFLAMMATORY DISORDERS, THE LITERATURE ENDORSES AN IMPORTANT POTENTIAL ROLE FOR EPIGENETICS IN CHRONIC PAIN. CONCLUSIONS: EPIGENETIC ANALYSIS MAY IDENTIFY MECHANISMS CRITICAL TO THE DEVELOPMENT OF CHRONIC PAIN AFTER INJURY, AND MAY PROVIDE NEW PATHWAYS AND TARGET MECHANISMS FOR FUTURE DRUG DEVELOPMENT AND INDIVIDUALIZED MEDICINE. 2012