1 1018 97 CIRCFHIT MODULATES GABAERGIC SYNAPTIC TRANSMISSION VIA REGULATING THE PARENTAL GENE FHIT EXPRESSION IN THE SPINAL DORSAL HORN IN A RAT MODEL OF NEUROPATHIC PAIN. EFFECTIVE TREATMENTS FOR NEUROPATHIC PAIN ARE LACKING DUE TO OUR LIMITED UNDERSTANDING OF THE MECHANISMS. THE CIRCRNAS ARE MAINLY ENRICHED IN THE CENTRAL NERVOUS SYSTEM. HOWEVER, THEIR FUNCTION IN VARIOUS PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS HAVE YET TO BE DETERMINED. HERE, WE IDENTIFIED CIRCFHIT, AN EXON-INTRON CIRCRNA EXPRESSED IN GABAERGIC NEURONS, WHICH REDUCED THE INHIBITORY SYNAPTIC TRANSMISSION IN THE SPINAL DORSAL HORN TO MEDIATE SPARED NERVE INJURY-INDUCED NEUROPATHIC PAIN. MOREOVER, WE FOUND THAT CIRCFHIT DECREASED THE EXPRESSION OF GAD65 AND INDUCED HYPEREXCITATION IN NK1R(+) NEURONS BY PROMOTING THE EXPRESSION OF ITS PARENTAL GENE FHIT IN CIS. MECHANISTICALLY, CIRCFHIT WAS DIRECTLY BOUND TO THE INTRONIC REGION OF FHIT, AND FORMED A CIRCFHIT/HNRNPK COMPLEX TO PROMOTE POL II PHOSPHORYLATION AND H2B MONOUBIQUITINATION BY RECRUITING CDK9 AND RNF40 TO THE FHIT INTRON. IN SUMMARY, WE REVEALED THAT THE EXON-INTRON CIRCFHIT CONTRIBUTES TO GABAERGIC NEURON-MEDIATED NK1R(+) NEURONAL HYPEREXCITATION AND NEUROPATHIC PAIN VIA REGULATING FHIT IN CIS. 2023 2 5495 26 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 3 635 30 BIOLOGICAL FUNCTION OF LONG NON-CODING RNA (LNCRNA) XIST. LONG NON-CODING RNAS (LNCRNAS) REGULATE GENE EXPRESSION IN A VARIETY OF WAYS AT EPIGENETIC, CHROMATIN REMODELING, TRANSCRIPTIONAL, AND TRANSLATIONAL LEVELS. ACCUMULATING EVIDENCE SUGGESTS THAT LNCRNA X-INACTIVE SPECIFIC TRANSCRIPT (LNCRNA XIST) SERVES AS AN IMPORTANT REGULATOR OF CELL GROWTH AND DEVELOPMENT. DESPITES ITS ORIGINAL ROLES IN X-CHROMOSOME DOSAGE COMPENSATION, LNCRNA XIST ALSO PARTICIPATES IN THE DEVELOPMENT OF TUMOR AND OTHER HUMAN DISEASES BY FUNCTIONING AS A COMPETING ENDOGENOUS RNA (CERNA). IN THIS REVIEW, WE COMPREHENSIVELY SUMMARIZED RECENT PROGRESS IN UNDERSTANDING THE CELLULAR FUNCTIONS OF LNCRNA XIST IN MAMMALIAN CELLS AND DISCUSSED CURRENT KNOWLEDGE REGARDING THE CERNA NETWORK OF LNCRNA XIST IN VARIOUS DISEASES. LONG NON-CODING RNAS (LNCRNAS) ARE TRANSCRIPTS THAT ARE MORE THAN 200 NT IN LENGTH AND WITHOUT AN APPARENT PROTEIN-CODING CAPACITY (FURLAN AND ROUGEULLE, 2016; MADURO ET AL., 2016). THESE RNAS ARE BELIEVED TO BE TRANSCRIBED BY THE APPROXIMATELY 98-99% NON-CODING REGIONS OF THE HUMAN GENOME (DERRIEN ET AL., 2012; FU, 2014; MONTALBANO ET AL., 2017; SLACK AND CHINNAIYAN, 2019), AS WELL AS A LARGE VARIETY OF GENOMIC REGIONS, SUCH AS EXONIC, TRONIC, AND INTERGENIC REGIONS. HENCE, LNCRNAS ARE ALSO DIVIDED INTO EIGHT CATEGORIES: INTERGENIC LNCRNAS, INTRONIC LNCRNAS, ENHANCER LNCRNAS, PROMOTER LNCRNAS, NATURAL ANTISENSE/SENSE LNCRNAS, SMALL NUCLEOLAR RNA-ENDED LNCRNAS (SNO-LNCRNAS), BIDIRECTIONAL LNCRNAS, AND NON-POLY(A) LNCRNAS (MA ET AL., 2013; DEVAUX ET AL., 2015; ST LAURENT ET AL., 2015; CHEN, 2016; QUINN AND CHANG, 2016; RICHARD AND EICHHORN, 2018; CONNERTY ET AL., 2020). A RANGE OF EVIDENCE HAS SUGGESTED THAT LNCRNAS FUNCTION AS KEY REGULATORS IN CRUCIAL CELLULAR FUNCTIONS, INCLUDING PROLIFERATION, DIFFERENTIATION, APOPTOSIS, MIGRATION, AND INVASION, BY REGULATING THE EXPRESSION LEVEL OF TARGET GENES VIA EPIGENOMIC, TRANSCRIPTIONAL, OR POST-TRANSCRIPTIONAL APPROACHES (CAO ET AL., 2018). MOREOVER, LNCRNAS DETECTED IN BODY FLUIDS WERE ALSO BELIEVED TO SERVE AS POTENTIAL BIOMARKERS FOR THE DIAGNOSIS, PROGNOSIS, AND MONITORING OF DISEASE PROGRESSION, AND ACT AS NOVEL AND POTENTIAL DRUG TARGETS FOR THERAPEUTIC EXPLOITATION IN HUMAN DISEASE (JIANG W. ET AL., 2018; ZHOU ET AL., 2019A). LONG NON-CODING RNA X-INACTIVE SPECIFIC TRANSCRIPT (LNCRNA XIST) ARE A SET OF 15,000-20,000 NT SEQUENCES LOCALIZED IN THE X CHROMOSOME INACTIVATION CENTER (XIC) OF CHROMOSOME XQ13.2 (BROWN ET AL., 1992; DEBRAND ET AL., 1998; KAY, 1998; LEE ET AL., 2013; DA ROCHA AND HEARD, 2017; YANG Z. ET AL., 2018; BROCKDORFF, 2019). PREVIOUS STUDIES HAVE INDICATED THAT LNCRNA XIST REGULATE X CHROMOSOME INACTIVATION (XCI), RESULTING IN THE INHERITABLE SILENCING OF ONE OF THE X-CHROMOSOMES DURING FEMALE CELL DEVELOPMENT. ALSO, IT SERVES A VITAL REGULATORY FUNCTION IN THE WHOLE SPECTRUM OF HUMAN DISEASE (NOTABLY CANCER) AND CAN BE USED AS A NOVEL DIAGNOSTIC AND PROGNOSTIC BIOMARKER AND AS A POTENTIAL THERAPEUTIC TARGET FOR HUMAN DISEASE IN THE CLINIC (LIU ET AL., 2018B; DENG ET AL., 2019; DINESCU ET AL., 2019; MUTZEL AND SCHULZ, 2020; PATRAT ET AL., 2020; WANG ET AL., 2020A). IN PARTICULAR, LNCRNA XIST HAVE BEEN DEMONSTRATED TO BE INVOLVED IN THE DEVELOPMENT OF MULTIPLE TYPES OF TUMORS INCLUDING BRAIN TUMOR, LEUKEMIA, LUNG CANCER, BREAST CANCER, AND LIVER CANCER, WITH THE PROMINENT EXAMPLES OUTLINED IN TABLE 1. IT WAS ALSO BELIEVED THAT LNCRNA XIST (CHALIGNE AND HEARD, 2014; YANG Z. ET AL., 2018) CONTRIBUTED TO OTHER DISEASES, SUCH AS PULMONARY FIBROSIS, INFLAMMATION, NEUROPATHIC PAIN, CARDIOMYOCYTE HYPERTROPHY, AND OSTEOARTHRITIS CHONDROCYTES, AND MORE SPECIFIC DETAILS CAN BE FOUND IN TABLE 2. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE ON THE REGULATORY MECHANISMS OF LNCRNA XIST ON BOTH CHROMOSOME DOSAGE COMPENSATION AND PATHOGENESIS (ESPECIALLY CANCER) PROCESSES, WITH A FOCUS ON THE REGULATORY NETWORK OF LNCRNA XIST IN HUMAN DISEASE. 2021 4 1147 21 CONDYLE MODELING STABILITY, CRANIOFACIAL ASYMMETRY AND ACTN3 GENOTYPES: CONTRIBUTION TO TMD PREVALENCE IN A COHORT OF DENTOFACIAL DEFORMITIES. CRANIOFACIAL ASYMMETRY, MANDIBULAR CONDYLAR MODELING AND TEMPOROMANDIBULAR JOINT DISORDERS ARE COMMON COMORBIDITIES OF SKELETALLY DISPROPORTIONATE MALOCCLUSIONS, BUT ETIOLOGY OF OCCURRENCE TOGETHER IS POORLY UNDERSTOOD. WE COMPARED ASYMMETRY, CONDYLE MODELING STABILITY AND TEMPOROMANDIBULAR HEALTH IN A COHORT OF 128 PATIENTS HAVING ORTHODONTICS AND ORTHOGNATHIC SURGERY TO CORRECT DENTOFACIAL DEFORMITY MALOCCLUSIONS. WE ALSO COMPARED ACTN3 AND ENPP1 GENOTYPES FOR ASSOCIATION TO CLINICAL CONDITIONS. PRE-SURGICAL POSTERIOR-ANTERIOR CEPHALOMETRIC AND PANOMETRIC RADIOGRAPHIC ANALYSES; JAW PAIN AND FUNCTION QUESTIONNAIRE AND CLINICAL EXAMINATION OF TMD; AND SNP-GENOTYPE ANALYSIS FROM SALIVA SAMPLES WERE COMPARED TO ASSESS INTERRELATIONSHIPS. ALMOST HALF HAD ASYMMETRIES IN NEED OF SURGICAL CORRECTION, WHICH COULD BE SUBDIVIDED INTO FOUR DISTINCT MORPHOLOGICAL PATTERNS. ASYMMETRIC CONDYLE MODELING BETWEEN SIDES WAS SIGNIFICANTLY GREATER IN CRANIOFACIAL ASYMMETRY, BUT MOST COMMONLY HAD AN UNANTICIPATED PATTERN. OFTEN, LONGER OR LARGER CONDYLES OCCURRED ON THE SHORTER MANDIBULAR RAMUS SIDE. SUBJECTS WITH LONGER RAMUS BUT DIMENSIONALLY SMALLER CONDYLES WERE MORE LIKELY TO HAVE SELF-REPORTED TMD SYMPTOMS (P = 0.023) AND SIGNIFICANTLY GREATER CLINICAL DIAGNOSIS OF TMD (P = 0 .000001), WITH MASTICATORY MYALGIA MOST PROMINENT. GENOTYPING FOUND TWO SIGNIFICANT GENOTYPE ASSOCIATIONS FOR ACTN3 RS1671064 (Q523R MISSENSE) P = 0.02; RS678397 (INTRONIC SNP) P = 0.04 AND ONE SIGNIFICANT ALLELE ASSOCIATION RS1815739 (R577X NONSENSE) P = 0.00. SKELETAL ASYMMETRY, UNUSUAL CONDYLE MODELING AND TMD ARE COMMON AND INTERRELATED COMPONENTS OF MANY DENTOFACIAL DEFORMITIES. IMBALANCED MUSCULOSKELETAL FUNCTIONAL ADAPTATIONS AND GENETIC OR EPIGENETIC INFLUENCES CONTRIBUTE TO THE ETIOLOGY, AND REQUIRE FURTHER INVESTIGATION. 2020 5 4946 27 PATERNAL PSYCHOLOGICAL STRESS REPROGRAMS HEPATIC GLUCONEOGENESIS IN OFFSPRING. BOTH EPIDEMIOLOGIC AND EXPERIMENTAL ANIMAL STUDIES DEMONSTRATE THAT CHRONIC PSYCHOLOGICAL STRESS EXERTS ADVERSE EFFECTS ON THE INITIATION AND/OR PROGRESSION OF MANY DISEASES. HOWEVER, INTERGENERATIONAL EFFECTS OF THIS ENVIRONMENTAL INFORMATION REMAINS POORLY UNDERSTOOD. HERE, USING A C57BL/6 MOUSE MODEL OF RESTRAINT STRESS, WE SHOW THAT OFFSPRING OF STRESSED FATHERS EXHIBIT HYPERGLYCEMIA DUE TO ENHANCED HEPATIC GLUCONEOGENESIS AND ELEVATED EXPRESSION OF PEPCK. MECHANISTICALLY, WE IDENTIFY AN EPIGENETIC ALTERATION AT THE PROMOTER REGION OF THE SFMBT2 GENE, A MATERNALLY IMPRINTED POLYCOMB GENE, LEADING TO A DOWNREGULATION OF INTRONIC MICRORNA-466B-3P, WHICH POST-TRANSCRIPTIONALLY INHIBITS PEPCK EXPRESSION. IMPORTANTLY, HYPERGLYCEMIA IN F1 MICE IS REVERSED BY RU486 TREATMENT IN FATHERS, AND DEXAMETHASONE ADMINISTRATION IN F0 MICE PHENOCOPIES THE ROLES OF RESTRAINT STRESS. THUS, WE PROVIDE EVIDENCE SHOWING THE EFFECTS OF PATERNAL PSYCHOLOGICAL STRESS ON THE REGULATION OF GLUCOSE METABOLISM IN OFFSPRING, WHICH MAY HAVE PROFOUND IMPLICATIONS FOR OUR UNDERSTANDING OF HEALTH AND DISEASE RISK INHERITED FROM FATHERS. 2016 6 5120 25 POSSIBLE EPIGENETIC REGULATORY EFFECT OF DYSREGULATED CIRCULAR RNAS IN EPILEPSY. CIRCULAR RNAS (CIRCRNAS) INVOLVE IN THE EPIGENETIC REGULATION AND ITS MAJOR MECHANISM IS THE SEQUESTRATION OF THE TARGET MICRO RNAS (MIRNAS). WE HYPOTHESIZED THAT CIRCRNAS MIGHT BE RELATED WITH THE PATHOPHYSIOLOGY OF CHRONIC EPILEPSY AND EVALUATED THE ALTERED CIRCRNA EXPRESSIONS AND THEIR POSSIBLE REGULATORY EFFECTS ON THEIR TARGET MIRNAS AND MRNAS IN A MOUSE EPILEPSY MODEL. THE CIRCRNA EXPRESSION PROFILE IN THE HIPPOCAMPUS OF THE PILOCARPINE MICE WAS ANALYZED AND COMPARED WITH CONTROL. THE CORRELATION BETWEEN THE EXPRESSION OF MIRNA BINDING SITES (MIRNA RESPONSE ELEMENTS, MRE) IN THE DYSREGULATED CIRCRNAS AND THE EXPRESSION OF THEIR TARGET MIRNAS WAS EVALUATED. AS MIRNAS ALSO INHIBIT THEIR TARGET MRNAS, CIRCRNA-MIRNA-MRNA REGULATORY NETWORK, COMPRISED OF DYSREGULATED RNAS THAT TARGETS ONE ANOTHER WERE SEARCHED. FOR THE IDENTIFIED NETWORKS, BIOINFORMATICS ANALYSES WERE PERFORMED. AS THE RESULT, FORTY-THREE CIRCRNAS WERE DYSREGULATED IN THE HIPPOCAMPUS (UP-REGULATED, 26; DOWN-REGULATED, 17). THE CHANGE IN THE EXPRESSION OF MRE IN THOSE CIRCRNAS NEGATIVELY CORRELATED WITH THE CHANGE IN THE RELEVANT TARGET MIRNA EXPRESSION (R = -0.461, P<0.001), SUPPORTING THAT CIRCRNAS INHIBIT THEIR TARGET MIRNA. 333 DYSREGULATED CIRCRNA-MIRNA-MRNA NETWORKS WERE IDENTIFIED. GENE ONTOLOGY AND PATHWAY ANALYSES DEMONSTRATED THAT THE UP-REGULATED MRNAS IN THOSE NETWORKS WERE CLOSELY RELATED TO THE MAJOR PROCESSES IN EPILEPSY. AMONG THEM, STRING ANALYSIS IDENTIFIED 37 KEY MRNAS WITH ABUNDANT (>/=4) INTERACTIONS WITH OTHER DYSREGULATED TARGET MRNAS. THE DYSREGULATION OF THE CIRCRNAS WHICH HAD MULTIPLE INTERACTIONS WITH KEY MRNAS WERE VALIDATED BY PCR. WE CONCLUDED THAT DYSREGULATED CIRCRNAS MIGHT HAVE A PATHOPHYSIOLOGIC ROLE IN CHRONIC EPILEPSY BY REGULATING MULTIPLE DISEASE RELEVANT MRNAS VIA CIRCRNA-MIRNA-MRNA INTERACTIONS. 2018 7 6855 17 [NEW APPROACH TO THE INVESTIGATION OF DOHAD USING X-INACTIVATION GENE EXPRESSION SYSTEM]. X-CHROMOSOME INACTIVATION (XCI) OCCURS DURING THE GESTATION PERIOD TO COMPENSATE FOR THE DOSAGE OF X-LINKED GENES IN FEMALE MAMMALS. XIST RNA IS A LONG NONCODING RNA WITH A GLOBAL EPIGENETIC FUNCTION AND IS INDISPENSABLE FOR XCI FROM THE INITIATION TO ESTABLISHMENT AND MAINTENANCE PHASES. THE X CHROMOSOME CONTAINS OVER 1,000 GENES THAT ARE ESSENTIAL FOR PROPER DEVELOPMENT, ESPECIALLY THAT OF THE BRAIN, IMMUNE SYSTEM, METABOLISM AND REPRODUCTIVE FUNCTIONS. WE FOUND THAT EXPOSURE TO BISPHENOL A OR FOLATE DEFICIENCY DURING THE FETAL PERIOD CHANGES THE EXPRESSIONS OF XIST, TSIX (THE ANTISENSE REPRESSOR OF XIST), AND MANY X CHROMOSOME LINKED GENES WIDELY IN NEWBORN MICE. THIS FINDING SUGGESTS THAT THIS X-CHROMOSOME MEDIATED EFFECT IS CONSIDERED ONE OF THE MECHANISMS OF VARIOUS PROBLEMS ENCOUNTERED IN THE FETAL ENVIRONMENT. THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HYPOTHESIS STATES THAT NUTRITION AND OTHER ENVIRONMENTAL STIMULI DURING CRITICAL PERIODS AFFECT DEVELOPMENTAL PATHWAYS WITH EPIGENETICS AND INDUCE METABOLISM AND CHRONIC DISEASE SUSCEPTIBILITY. THE XCI PROCESS HAS SOME SIMILARITIES TO THIS HYPOTHESIS AND IT MAY BECOME ONE OF THE APPROACHES TO REVEAL THE DOHAD MECHANISMS. 2018 8 60 27 A GENOME-WIDE SCREEN REVEALS MICRORNAS IN PERIPHERAL SENSORY NEURONS DRIVING PAINFUL DIABETIC NEUROPATHY. DIABETES IS A LEADING CAUSE OF PERIPHERAL NEUROPATHY (DIABETIC PERIPHERAL NEUROPATHY, DPN), AND UNCONTROLLED LONG-LASTING HYPERGLYCEMIA LEADS TO SEVERE COMPLICATIONS. A MAJOR PROPORTION OF DIABETICS DEVELOP EXCRUCIATING PAIN WITH A VARIABLE COURSE. MECHANISMS LEADING TO PAINFUL DPN ARE NOT COMPLETELY UNDERSTOOD AND TREATMENT OPTIONS LIMITED. WE HYPOTHESIZED THAT EPIGENETIC MODULATION AT THE LEVEL OF MICRORNA (MIRNA) EXPRESSION TRIGGERED BY METABOLIC IMBALANCE AND NERVE DAMAGE REGULATES THE COURSE OF PAIN DEVELOPMENT. WE USED CLINICALLY RELEVANT PRECLINICAL MODELS, GENOME-WIDE SCREENING, IN SILICO ANALYSES, CELLULAR ASSAYS, MIRNA FLUORESCENT IN SITU HYBRIDIZATION, IN VIVO MOLECULAR MANIPULATIONS, AND BEHAVIORAL ANALYSES IN THE CURRENT STUDY. WE IDENTIFIED MIRNAS AND THEIR TARGETS THAT CRITICALLY IMPACT ON NOCICEPTIVE HYPERSENSITIVITY IN PAINFUL DPN. OUR ANALYSES IDENTIFY MIR-33 AND MIR-380 EXPRESSED IN NOCICEPTIVE NEURONS AS CRITICAL DENOMINATORS OF DIABETIC PAIN AND MIR-124-1 AS A MEDIATOR OF PHYSIOLOGICAL NOCICEPTION. OUR COMPREHENSIVE ANALYSES ON THE PUTATIVE MRNA TARGETS FOR MIR-33 OR MIR-124-1 IDENTIFIED A SET OF MRNAS THAT ARE REGULATED AFTER MIR-33 OR MIR-124-1 OVEREXPRESSION IN DORSAL ROOT GANGLIA IN VIVO. OUR RESULTS SHED LIGHT ON THE REGULATION OF DPN PATHOPHYSIOLOGY AND IMPLICATE SPECIFIC MIRNAS AS NOVEL THERAPEUTIC TARGETS FOR TREATING PAINFUL DPN. 2021 9 6907 23 [THE ROLE OF THE CIRCULAR RNAS IN MULTIPLE SCLEROSIS AND OTHER NEUROIMMUNE DISORDERS]. IN RECENT YEARS NON-CODING RNAS HAVE RECEIVED INCREASING ATTENTION AS AN IMPORTANT EPIGENETIC MECHANISM, WITH PARTICULAR ROLE OF MICRO RNAS. AS THE REGULATION OF MIRNA EXPRESSION IS HIGHLY DYNAMIC AND COMPLEX, GROWING EVIDENCE SUGGESTS THE EXISTENCE OF ANOTHER HIGHER LEVEL OF REGULATORY MECHANISM INVOLVED IN MIRNA ACTIVITY - CIRCULAR RNAS (CIRCRNAS). CIRCRNAS REPRESENT NOVEL, UNIQUE CLASS OF ENDOGENOUS NCRNAS CONTROLLING THE EXPRESSION AND FUNCTION OF MIRNA. THEY ARE CALLED NATURAL MIRNA "SPONGES". ACCUMULATING EVIDENCE REVEALS CIRCRNAS ROLE IN PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES INCLUDING CNS AND IMMUNE REGULATION. PREVIOUS STUDIES IMPLICATED MIRNAS IN REGULATION OF AUTOIMMUNE DEMYELINATION IN MS. MULTIPLE SCLEROSIS IS A CHRONIC NEUROLOGICAL INFLAMMATORY DEMYELINATING DISORDER OF THE CENTRAL NERVOUS SYSTEM. WHILE THE ETIOLOGY OF MS IS STILL NOT FULLY UNDERSTOOD, ACCUMULATING EVIDENCE SUGGESTS THAT IT IS A MULTIFACTORIAL ENTITY WITH SIGNIFICANT INVOLVEMENT OF AUTOIMMUNE PROCESSES. 2022 10 263 17 ADVANCES WITH LONG NON-CODING RNAS IN DIABETIC PERIPHERAL NEUROPATHY. LONG NON-CODING RNAS (?LNCRNAS) ?ARE A GROUP OF NON-CODING RNAS LONGER THAN 200 NUCLEOTIDES, WHICH ARE DEFINED AS TRANSCRIPTS. THE LNCRNAS ARE INVOLVED IN REGULATING GENE EXPRESSION AT EPIGENETIC, TRANSCRIPTIONAL, AND POST-TRANSCRIPTIONAL LEVELS. RECENT STUDIES HAVE FOUND THAT LNCRNA IS CLOSELY RELATED TO MANY DISEASES LIKE NEUROLOGICAL DISEASES, ENDOCRINE AND METABOLIC DISORDERS. DIABETIC PERIPHERAL NEUROPATHY (DPN) IS ONE OF THE MOST COMMON CHRONIC COMPLICATIONS OF DIABETES MELLITUS. IN THIS REVIEW, WE HIGHLIGHT THE LATEST RESEARCH RELATED TO LNCRNAS IN DPN. 2020 11 4338 24 MICROVASCULAR BARRIER PROTECTION BY MICRORNA-183 VIA FOXO1 REPRESSION: A PATHWAY DISTURBED IN NEUROPATHY AND COMPLEX REGIONAL PAIN SYNDROME. BLOOD NERVE BARRIER DISRUPTION AND EDEMA ARE COMMON IN NEUROPATHIC PAIN AS WELL AS IN COMPLEX REGIONAL PAIN SYNDROME (CRPS). MICRORNAS (MIRNA) ARE EPIGENETIC MULTITARGET SWITCHES CONTROLLING NEURONAL AND NON-NEURONAL CELLS IN PAIN. THE MIR-183 COMPLEX ATTENUATES HYPEREXCITABILITY IN NOCICEPTORS, BUT ADDITIONAL NON-NEURONAL EFFECTS VIA TRANSCRIPTION FACTORS COULD CONTRIBUTE AS WELL. THIS STUDY EXPLORED EXOSOMAL MIR-183 IN CRPS AND MURINE NEUROPATHY, ITS EFFECT ON THE MICROVASCULAR BARRIER VIA TRANSCRIPTION FACTOR FOXO1 AND TIGHT JUNCTION PROTEIN CLAUDIN-5, AND ITS ANTIHYPERALGESIC POTENTIAL. SCIATIC MIR-183 DECREASED AFTER CCI. SUBSTITUTION WITH PERINEURAL MIR-183 MIMIC ATTENUATED MECHANICAL HYPERSENSITIVITY AND RESTORED BLOOD NERVE BARRIER FUNCTION. IN VITRO, SERUM FROM CCI MICE UND CRPS PATIENTS WEAKENED THE MICROVASCULAR BARRIER OF MURINE CEREBELLAR ENDOTHELIAL CELLS, INCREASED ACTIVE FOXO1 AND REDUCED CLAUDIN-5, CONCOMITANT WITH A LACK OF EXOSOMAL MIR-183 IN CRPS PATIENTS. CELLULAR STRESS ALSO COMPROMISED THE MICROVASCULAR BARRIER WHICH WAS RESCUED EITHER BY MIR-183 MIMIC VIA FOXO1 REPRESSION OR BY PRIOR SILENCING OF FOXO1. PERSPECTIVE: LOW MIR-183 LEADING TO BARRIER IMPAIRMENT VIA FOXO1 AND SUBSEQUENT CLAUDIN-5 SUPPRESSION IS A NEW ASPECT IN THE PATHOPHYSIOLOGY OF CRPS AND NEUROPATHIC PAIN. THIS PATHWAY MIGHT HELP UNTANGLE THE WIDE SYMPTOMATIC RANGE OF CRPS AND NURTURE FURTHER RESEARCH INTO MIRNA MIMICS OR FOXO1 INHIBITORS. 2022 12 124 21 A SYSTEMS APPROACH DELIVERS A FUNCTIONAL MICRORNA CATALOG AND EXPANDED TARGETS FOR SEIZURE SUPPRESSION IN TEMPORAL LOBE EPILEPSY. TEMPORAL LOBE EPILEPSY IS THE MOST COMMON DRUG-RESISTANT FORM OF EPILEPSY IN ADULTS. THE REORGANIZATION OF NEURAL NETWORKS AND THE GENE EXPRESSION LANDSCAPE UNDERLYING PATHOPHYSIOLOGIC NETWORK BEHAVIOR IN BRAIN STRUCTURES SUCH AS THE HIPPOCAMPUS HAS BEEN SUGGESTED TO BE CONTROLLED, IN PART, BY MICRORNAS. TO SYSTEMATICALLY ASSESS THEIR SIGNIFICANCE, WE SEQUENCED ARGONAUTE-LOADED MICRORNAS TO DEFINE FUNCTIONALLY ENGAGED MICRORNAS IN THE HIPPOCAMPUS OF THREE DIFFERENT ANIMAL MODELS IN TWO SPECIES AND AT SIX TIME POINTS BETWEEN THE INITIAL PRECIPITATING INSULT THROUGH TO THE ESTABLISHMENT OF CHRONIC EPILEPSY. WE THEN SELECTED COMMONLY UP-REGULATED MICRORNAS FOR A FUNCTIONAL IN VIVO THERAPEUTIC SCREEN USING OLIGONUCLEOTIDE INHIBITORS. ARGONAUTE SEQUENCING GENERATED 1.44 BILLION SMALL RNA READS OF WHICH UP TO 82% WERE MICRORNAS, WITH OVER 400 UNIQUE MICRORNAS DETECTED PER MODEL. APPROXIMATELY HALF OF THE DETECTED MICRORNAS WERE DYSREGULATED IN EACH EPILEPSY MODEL. WE PRIORITIZED COMMONLY UP-REGULATED MICRORNAS THAT WERE FULLY CONSERVED IN HUMANS AND DESIGNED CUSTOM ANTISENSE OLIGONUCLEOTIDES FOR THESE CANDIDATE TARGETS. ANTISEIZURE PHENOTYPES WERE OBSERVED UPON KNOCKDOWN OF MIR-10A-5P, MIR-21A-5P, AND MIR-142A-5P AND ELECTROPHYSIOLOGICAL ANALYSES INDICATED BROAD SAFETY OF THIS APPROACH. COMBINED INHIBITION OF THESE THREE MICRORNAS REDUCED SPONTANEOUS SEIZURES IN EPILEPTIC MICE. PROTEOMIC DATA, RNA SEQUENCING, AND PATHWAY ANALYSIS ON PREDICTED AND VALIDATED TARGETS OF THESE MICRORNAS IMPLICATED DEREPRESSED TGF-BETA SIGNALING AS A SHARED SEIZURE-MODIFYING MECHANISM. CORRESPONDINGLY, INHIBITION OF TGF-BETA SIGNALING OCCLUDED THE ANTISEIZURE EFFECTS OF THE ANTAGOMIRS. TOGETHER, THESE RESULTS IDENTIFY SHARED, DYSREGULATED, AND FUNCTIONALLY ACTIVE MICRORNAS DURING THE PATHOGENESIS OF EPILEPSY WHICH REPRESENT THERAPEUTIC ANTISEIZURE TARGETS. 2020 13 1878 13 EMERGING ROLES OF LONG NONCODING RNA IN CHONDROGENESIS, OSTEOGENESIS, AND OSTEOARTHRITIS. OSTEOARTHRITIS (OA) IS THE MOST PREVALENT AGE-RELATED DEBILITATING JOINT DISEASE, AND IS CHARACTERIZED PRIMARILY BY ARTICULAR CARTILAGE DEGRADATION AND SUBCHONDRAL BONE LESIONS. IT IS ALSO THE LEADING CAUSE OF CHRONIC MORBIDITY IN OLDER POPULATIONS. THE ETIOLOGY OF OA IS MULTIFACTORIAL, WITH THE UNDERLYING REGULATORY MECHANISMS REMAINING LARGELY UNKNOWN. LONG NONCODING RNA (LNCRNA) IS A GROUP OF NONCODING RNAS DEFINED AS BEING >200 NUCLEOTIDES IN LENGTH. INCREASING EVIDENCE DEMONSTRATES THAT MANY LNCRNAS SERVE AS CRITICAL REGULATORS OF CHONDROGENESIS AND BONE AND CARTILAGE HOMEOSTASIS, THEREBY INFLUENCING OA DEVELOPMENT. IN THIS REVIEW, WE HIGHLIGHT THE CURRENT UNDERSTANDING CONCERNING LNCRNAS, INCLUDING THEIR PHYSICAL FEATURES, BIOLOGICAL FUNCTIONS, AND POTENTIAL ROLES IN CHONDROGENESIS, OSTEOGENESIS, AND OA. THIS INFORMATION MAY SHED NEW LIGHT ON THE EPIGENETIC REGULATION OF CARTILAGE AND SUBSTANTIATE LNCRNAS AS NOVEL THERAPEUTIC TARGETS IN OA. 2019 14 4713 29 NON-CODING RNA AND N6-METHYLADENOSINE MODIFICATION PLAY CRUCIAL ROLES IN NEUROPATHIC PAIN. AFTER PERIPHERAL NERVE INJURY, PAIN SIGNALS ARE TRANSMITTED FROM PRIMARY SENSORY NEURONS IN THE DORSAL ROOT GANGLION (DRG) TO THE CENTRAL NERVOUS SYSTEM. EPIGENETIC MODIFICATION AFFECTS NEUROPATHIC PAIN THROUGH ALTERATIONS IN THE GENE EXPRESSION IN PAIN-RELATED AREAS AND GLIAL CELL ACTIVATION. RECENT STUDIES HAVE SHOWN THAT NON-CODING RNA AND N6-METHYLADENOSINE (M6A) METHYLATION MODIFICATION PLAY PIVOTAL REGULATORY ROLES IN THE OCCURRENCE AND MAINTENANCE OF NEUROPATHIC PAIN. DYSREGULATION OF THE RNA M6A LEVEL VIA DYNAMIC CHANGES IN METHYLTRANSFERASE AND DEMETHYLASE AFTER CENTRAL OR PERIPHERAL NERVE INJURY COMMONLY REGULATES PAIN-ASSOCIATED GENES, CONTRIBUTING TO THE INDUCTION AND MAINTENANCE OF NEUROPATHIC PAIN. THE DYNAMIC PROCESS HAS SIGNIFICANT IMPLICATIONS FOR THE DEVELOPMENT AND MAINTENANCE OF NEUROPATHIC PAIN. HOWEVER, THE UNDERLYING MECHANISMS BY WHICH NON-CODING RNA AND M6A RNA MODIFICATION REGULATE NEUROPATHIC PAIN ARE NOT WELL-CHARACTERIZED. THIS ARTICLE ELUCIDATES THE MULTIPLE MECHANISMS OF NON-CODING RNA AND M6A METHYLATION IN THE CONTEXT OF NEUROPATHIC PAIN, AND SUMMARIZES ITS POTENTIAL FUNCTIONS AS WELL AS RECENT ADVANCES. 2022 15 2876 20 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 16 1021 20 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 17 1131 28 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 18 2179 31 EPIGENETIC MECHANISMS OF NEURAL PLASTICITY IN CHRONIC NEUROPATHIC PAIN. NEUROPATHIC PAIN IS A CHALLENGING CLINICAL PROBLEM AND REMAINS DIFFICULT TO TREAT. ALTERED GENE EXPRESSION IN PERIPHERAL SENSORY NERVES AND NEURONS DUE TO NERVE INJURY IS WELL DOCUMENTED AND CONTRIBUTES CRITICALLY TO THE SYNAPTIC PLASTICITY IN THE SPINAL CORD AND THE INITIATION AND MAINTENANCE OF CHRONIC PAIN. HOWEVER, OUR UNDERSTANDING OF THE EPIGENETIC MECHANISMS REGULATING THE TRANSCRIPTION OF PRO-NOCICEPTIVE (E.G., NMDA RECEPTORS AND ALPHA2DELTA-1) AND ANTINOCICEPTIVE (E.G., POTASSIUM CHANNELS AND OPIOID AND CANNABINOID RECEPTORS) GENES ARE STILL LIMITED. IN THIS REVIEW, WE SUMMARIZE RECENT STUDIES DETERMINING THE ROLES OF HISTONE MODIFICATIONS (INCLUDING METHYLATION, ACETYLATION, AND UBIQUITINATION), DNA METHYLATION, AND NONCODING RNAS IN NEUROPATHIC PAIN DEVELOPMENT. WE REVIEW THE EPIGENETIC WRITER, READER, AND ERASER PROTEINS THAT PARTICIPATE IN THE TRANSCRIPTIONAL CONTROL OF THE EXPRESSION OF KEY ION CHANNELS AND NEUROTRANSMITTER RECEPTORS IN THE DORSAL ROOT GANGLION AFTER TRAUMATIC NERVE INJURY, WHICH IS COMMONLY USED AS A PRECLINICAL MODEL OF NEUROPATHIC PAIN. A BETTER UNDERSTANDING OF EPIGENETIC REPROGRAMMING INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN COULD LEAD TO THE DEVELOPMENT OF NEW TREATMENTS FOR NEUROPATHIC PAIN. 2022 19 4259 40 METTL3 SUPPRESSES NEUROPATHIC PAIN VIA MODULATING N6-METHYLADENOSINE-DEPENDENT PRIMARY MIR-150 PROCESSING. METHYLTRANSFERASE-LIKE 3 (METTL3)-MODULATED N6-METHYLADENOSINE (M6A) WAS RECENTLY IDENTIFIED AS AN IMPORTANT EPIGENETIC REGULATION TYPE DURING RNA PROCESSING AND CONTRIBUTES TO MULTIPLE PATHOLOGICAL PROCESSES. NEUROPATHIC PAIN (NP) IS INDUCED BY A LESION OF THE SOMATOSENSORY NERVOUS SYSTEM, AND THE DETAILED PATHWAYS BY WHICH METTL3/M6A REGULATED TO MODULATE GENE DYSREGULATION AND ENABLE NP HAVE REMAINED UNCLEAR. THEREFORE, THIS STUDY INVESTIGATED THE FUNCTION OF METTL3-MEDIATED M6A METHYLATION ON MIRNA MATURATION, AND INVESTIGATED HOW THIS REGULATION CONTRIBUTES TO NP PROGRESSION. A RAT MODEL CHARACTERIZED WITH TYPICAL NP WAS ESTABLISHED BY A SPARED NERVE-INJURY (SNI) METHOD. BY ANALYZING THE EXPRESSION LEVELS OF METTL3 AND M6A METHYLATION, WE FOUND THAT METTL3, ALONG WITH M6A METHYLATION, WAS DRAMATICALLY DOWNREGULATED IN NP RATS IN CONTRAST TO THE SHAM ONES. FUNCTIONALLY, ENHANCED METTL3 PROMOTED THE M6A METHYLATION IN TOTAL RNAS AND INHIBITED NP PROGRESSION, WHEREAS SILENCING METTL3 SUPPRESSED M6A METHYLATION AND INCREASED NP SEVERITY. MECHANISTICALLY, METTL3 ACCELERATED MIR-150 MATURATION VIA MEDIATING M6A METHYLATION OF PRIMIR-150 AT LOCUS 498, COOPERATING WITH THE "M6A READER" YTHDF2. MEANWHILE, MIR-150 COULD DIRECTLY TARGET BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) MRNA, AND THE METTL3/MIR-150/BDNF REGULATORY PATHWAY WAS FINALLY ESTABLISHED. CLINICALLY, WE PROVED THAT SERUM METTL3 MRNA WAS ALSO DOWNREGULATED IN SHINGLES PATIENTS WITH NP, SUGGESTING ITS DIAGNOSTIC POTENTIAL. IN CONCLUSION, WE DEMONSTRATED AN ESSENTIAL FUNCTION OF METTL3-REGULATED N6-METHYLADENOSINE DURING NP PROGRESSION VIA MODULATING PRIMIR-150 MATURATION. SERUM METTL3 COULD EFFECTIVELY DIFFERENTIATE NP PATIENTS FROM HEALTHY PEOPLE, AND IS USEFUL FOR DYNAMIC MONITORING OF DISEASES AFTER TREATMENT. THEREFORE, THE METTL3/MIR-150/BDNF PATHWAY MAY BE A PROMISING THERAPEUTIC TARGET FOR NP PATIENTS. 2022 20 1718 18 DYSREGULATED LONG NON-CODING RNAS IN THE TEMPORAL LOBE EPILEPSY MOUSE MODEL. PURPOSE: TO PERFORM COMPREHENSIVE PROFILING OF LONG NON-CODING RNAS (LNCRNAS) IN TEMPORAL LOBE EPILEPSY. METHODS: WE PERFORMED EXTENSIVE PROFILING OF LNCRNAS AND MRNAS IN THE MOUSE PILOCARPINE MODEL IN SPECIFIC BRAIN REGIONS, THE HIPPOCAMPUS AND CORTEX, AND COMPARED THE RESULTS TO THOSE OF THE CONTROL MOUSE. DIFFERENTIALLY EXPRESSED LNCRNAS AND MRNAS WERE IDENTIFIED WITH A MICROARRAY ANALYSIS (ARRAYSTAR MOUSE LNCRNA EXPRESSION MICROARRAY V3.0). THEN, GENE ONTOLOGY (GO) AND PATHWAY ANALYSIS WERE PERFORMED TO INVESTIGATE THE POTENTIAL ROLES OF THE DIFFERENTIALLY EXPRESSED MRNAS IN THE PILOCARPINE MODEL. PROTEIN-PROTEIN INTERACTIONS TRANSCRIBED BY DYSREGULATED MRNAS WITH/WITHOUT CO-DYSREGULATED LNCRNAS WERE ANALYZED USING STRING V10 (HTTP://STRING-DB.ORG/). RESULTS: A TOTAL OF 22 AND 83 LNCRNAS WERE UP- AND DOWN-REGULATED (>/=2.0-FOLD, ALL P < .05), RESPECTIVELY, IN THE HIPPOCAMPUS OF THE EPILEPSY MODEL, WHILE 46 AND 659 LNCRNAS WERE UP- AND DOWN-REGULATED, RESPECTIVELY, IN THE CORTEX OF THE EPILEPSY MODEL. GO AND PATHWAY ANALYSIS REVEALED THAT THE DYSREGULATED MRNAS WERE CLOSELY ASSOCIATED WITH A PROCESS ALREADY KNOWN TO BE INVOLVED IN EPILEPTOGENESIS: ACUTE INFLAMMATION, CALCIUM ION REGULATION, EXTRACELLULAR MATRIX REMODELING, AND NEURONAL DIFFERENTIATION. AMONG THE LNCRNAS, WE IDENTIFIED 10 LNCRNAS COMMONLY DYSREGULATED WITH CORRESPONDING MRNAS IN THE CORTEX. THE STRING ANALYSIS SHOWED THAT THE DYSREGULATED MRNAS WERE INTERCONNECTED AROUND TWO CENTERS: THE MTOR PATHWAY-RELATED GENES AND REST PATHWAY-RELATED GENES. CONCLUSION: LNCRNAS WERE DYSREGULATED IN THE PILOCARPINE MOUSE MODEL ACCORDING TO THE BRAIN REGIONS OF THE HIPPOCAMPUS AND CORTEX. THE DYSREGULATED LNCRNAS WITH CO-DYSREGULATED MRNAS MIGHT BE POSSIBLE THERAPEUTIC TARGETS FOR THE EPIGENETIC REGULATION OF CHRONIC EPILEPSY. 2018