{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:00:55Z","timestamp":1790438455805,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,30]],"date-time":"2019-11-30T00:00:00Z","timestamp":1575072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Autonoma della Sardegna\u201d, L.R. 7, 2007, 2013 call.","award":["Project ID: CRP-79506 a"],"award-info":[{"award-number":["Project ID: CRP-79506 a"]}]},{"name":"Fondo integrativo per la ricerca (Fir)","award":["Annualit\u00e0 2018"],"award-info":[{"award-number":["Annualit\u00e0 2018"]}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","award":["Fellowship"],"award-info":[{"award-number":["Fellowship"]}],"id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lithium is the mainstay in the maintenance of bipolar disorder (BD) and the most efficacious pharmacological treatment in suicide prevention. Nevertheless, its use is hampered by a high interindividual variability and important side effects. Genetic and epigenetic factors have been suggested to modulate lithium response, but findings so far have not allowed identifying molecular targets with predictive value. In this study we used next generation sequencing to measure genome-wide miRNA expression in lymphoblastoid cell lines from BD patients excellent responders (ER, n = 12) and non-responders (NR, n = 12) to lithium. These data were integrated with microarray genome-wide expression data to identify pairs of miRNA\/mRNA inversely and significantly correlated. Significant pairs were prioritized based on strength of association and in-silico miRNA target prediction analyses to select candidates for validation with qRT-PCR. Thirty-one miRNAs were differentially expressed in ER vs. NR and inversely correlated with 418 genes differentially expressed between the two groups. A total of 331 of these correlations were also predicted by in-silico algorithms. miR-320a and miR-155-3p, as well as three of their targeted genes (CAPNS1 (Calpain Small Subunit 1) and RGS16 (Regulator of G Protein Signaling 16) for miR-320, SP4 (Sp4 Transcription Factor) for miR-155-3p) were validated. These miRNAs and mRNAs were previously implicated in psychiatric disorders (miR-320a and SP4), key processes of the central nervous system (CAPNS1, RGS16, SP4) or pathways involved in mental illnesses (miR-155-3p). Using an integrated approach, we identified miRNAs and their targeted genes potentially involved in lithium response in BD.<\/jats:p>","DOI":"10.3390\/ijms20236040","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T10:50:45Z","timestamp":1575283845000},"page":"6040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-4319","authenticated-orcid":false,"given":"Claudia","family":"Pisanu","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Merkouri Papadima","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Melis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Congiu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Loizedda","sequence":"additional","affiliation":[{"name":"Consiglio Nazionale delle Ricerche (C.N.R.), Istituto di Ricerca Genetica e Biomedica (I.R.G.B.), Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Orr\u00f9","sequence":"additional","affiliation":[{"name":"Medical Genetics, R. Binaghi Hospital, ASSL Cagliari, ATS Sardegna, 09021 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-7995","authenticated-orcid":false,"given":"Stefano","family":"Calza","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, Italy"},{"name":"Big &amp; Open Data Innovation Laboratory, University of Brescia, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Orr\u00f9","sequence":"additional","affiliation":[{"name":"Medical Genetics, R. Binaghi Hospital, ASSL Cagliari, ATS Sardegna, 09021 Cagliari, Italy"},{"name":"Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-1579","authenticated-orcid":false,"given":"Carlo","family":"Carcassi","sequence":"additional","affiliation":[{"name":"Medical Genetics, R. Binaghi Hospital, ASSL Cagliari, ATS Sardegna, 09021 Cagliari, Italy"},{"name":"Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Severino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Ardau","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pharmacology of the University Hospital of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Chillotti","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pharmacology of the University Hospital of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-5938","authenticated-orcid":false,"given":"Maria","family":"Del Zompo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"},{"name":"Unit of Clinical Pharmacology of the University Hospital of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7415-7607","authenticated-orcid":false,"given":"Alessio","family":"Squassina","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0140-6736(15)00241-X","article-title":"Bipolar disorder","volume":"387","author":"Grande","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bdi.12165","article-title":"Cost of illness for bipolar disorder: A systematic review of the economic burden","volume":"16","author":"Touil","year":"2014","journal-title":"Bipolar Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/mp.2015.4","article-title":"Lithium in the treatment of bipolar disorder: Pharmacology and pharmacogenetics","volume":"20","author":"Alda","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s40261-017-0531-2","article-title":"Treatment of Bipolar Disorder in a Lifetime Perspective: Is Lithium Still the Best Choice?","volume":"37","author":"Sani","year":"2017","journal-title":"Clin. Drug Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1001\/archpsyc.57.2.187","article-title":"Does lithium treatment still work? Evidence of stable responses over three decades","volume":"57","author":"Baldessarini","year":"2000","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jad.2007.03.003","article-title":"Prophylactic treatment response in bipolar disorder: Results of a naturalistic observation study","volume":"104","author":"Garnham","year":"2007","journal-title":"J. Affect. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.2174\/1745017901612010142","article-title":"Does the \u201cSilver Bullet\u201c Lose its Shine Over the Time? Assessment of Loss of Lithium Response in a Preliminary Sample of Bipolar Disorder Outpatients","volume":"12","author":"Fornaro","year":"2016","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jad.2018.02.085","article-title":"Clinical and psychopathological features associated with treatment-emergent mania in bipolar-II depressed outpatients exposed to antidepressants","volume":"234","author":"Fornaro","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0165-0327(98)00160-8","article-title":"Clinical correlates of therapeutic response in bipolar disorder","volume":"67","author":"Bowden","year":"2001","journal-title":"J. Affect. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24S","DOI":"10.1097\/00004714-199604001-00004","article-title":"Predictors of response to mood stabilizers","volume":"16","author":"Calabrese","year":"1996","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.psychres.2018.08.034","article-title":"The identification of biomarkers predicting acute and maintenance lithium treatment response in bipolar disorder: A plea for further research attention","volume":"269","author":"Fornaro","year":"2018","journal-title":"Psychiatry Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1192\/S000712500029243X","article-title":"The challenge of predicting response to stabilising lithium treatment. The importance of patient selection","volume":"21","author":"Grof","year":"1993","journal-title":"Br. J. Psychiatry Suppl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1399-5618.2005.00244.x","article-title":"Which clinical factors predict response to prophylactic lithium? A systematic review for bipolar disorders","volume":"7","author":"Kleindienst","year":"2005","journal-title":"Bipolar Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.euroneuro.2017.02.001","article-title":"Pharmacogenomic aspects of bipolar disorder: An update","volume":"27","author":"Budde","year":"2017","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s40291-018-0335-y","article-title":"The Role of Pharmacogenomics in Bipolar Disorder: Moving Towards Precision Medicine","volume":"22","author":"Pisanu","year":"2018","journal-title":"Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(16)00143-4","article-title":"Genetic variants associated with response to lithium treatment in bipolar disorder: A genome-wide association study","volume":"387","author":"Hou","year":"2016","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.neulet.2016.06.045","article-title":"Understanding the molecular mechanisms underlying mood stabilizer treatments in bipolar disorder: Potential involvement of epigenetics","volume":"669","author":"Pisanu","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41580-018-0045-7","article-title":"Regulation of microRNA function in animals","volume":"20","author":"Gebert","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1017\/S1461145709000029","article-title":"MicroRNA expression changes in lymphoblastoid cell lines in response to lithium treatment","volume":"12","author":"Chen","year":"2009","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jad.2014.03.047","article-title":"MiRNA-206 and BDNF genes interacted in bipolar I disorder","volume":"162","author":"Wang","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e504","DOI":"10.1038\/tp.2014.139","article-title":"Novel integrative genomic tool for interrogating lithium response in bipolar disorder","volume":"5","author":"Hunsberger","year":"2015","journal-title":"Transl. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3389\/fpsyt.2018.00207","article-title":"Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder","volume":"9","author":"Reinbold","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2013.04.004","article-title":"Insulin-like growth factor 1 (IGF-1) expression is up-regulated in lymphoblastoid cell lines of lithium responsive bipolar disorder patients","volume":"73","author":"Squassina","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jpsychires.2015.07.023","article-title":"Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls","volume":"69","author":"Camkurt","year":"2015","journal-title":"J. Psychiatr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e14332","DOI":"10.1097\/MD.0000000000014332","article-title":"Screening of schizophrenia associated miRNAs and the regulation of miR-320a-3p on integrin beta1","volume":"98","author":"Wang","year":"2019","journal-title":"Medicine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mundalil Vasu, M., Anitha, A., Takahashi, T., Thanseem, I., Iwata, K., Asakawa, T., and Suzuki, K. (2016). Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164425"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jad.2013.12.035","article-title":"Identification of suitable plasma-based reference genes for miRNAome analysis of major depressive disorder","volume":"163","author":"Liu","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1523\/JNEUROSCI.4247-12.2013","article-title":"Conditional disruption of calpain in the CNS alters dendrite morphology, impairs LTP, and promotes neuronal survival following injury","volume":"33","author":"Amini","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.tins.2016.01.007","article-title":"Calpain-1 and Calpain-2: The Yin and Yang of Synaptic Plasticity and Neurodegeneration","volume":"39","author":"Baudry","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15533","DOI":"10.1073\/pnas.0507666102","article-title":"Comparative gene expression analysis of blood and brain provides concurrent validation of SELENBP1 up-regulation in schizophrenia","volume":"102","author":"Glatt","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lee, S.A., and Huang, K.C. (2016). Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia. BMC Med. Genom., 9.","DOI":"10.1186\/s12920-016-0229-y"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1507\/endocrj.EJ17-0130","article-title":"G-protein-coupled receptor signaling through Gpr176, Gz, and RGS16 tunes time in the center of the circadian clock [Review]","volume":"64","author":"Goto","year":"2017","journal-title":"Endocr. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/pcn.12688","article-title":"Circadian rhythm in bipolar disorder: A review of the literature","volume":"72","author":"Takaesu","year":"2018","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41386-018-0273-8","article-title":"Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder","volume":"44","author":"McCarthy","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1007\/s12031-015-0567-9","article-title":"Preliminary Transcriptome Analysis in Lymphoblasts from Cluster Headache and Bipolar Disorder Patients Implicates Dysregulation of Circadian and Serotonergic Genes","volume":"56","author":"Costa","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1080\/15622975.2017.1282174","article-title":"Lithium response in bipolar disorders and core clock genes expression","volume":"19","author":"Geoffroy","year":"2018","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.2217\/pgs.15.106","article-title":"A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis","volume":"16","author":"Higgins","year":"2015","journal-title":"Pharmacogenomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/bdi.12624","article-title":"Genetic polymorphisms associated with circadian rhythm dysregulation provide new perspectives on bipolar disorder","volume":"20","author":"Oliveira","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s12031-017-0938-5","article-title":"Evidence towards RNA Binding Motif (RNP1, RRM) Protein 3 (RBM3) as a Potential Biomarker of Lithium Response in Bipolar Disorder Patients","volume":"62","author":"Papadima","year":"2017","journal-title":"J. Mol. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1080\/15622975.2017.1346281","article-title":"Involvement of core clock genes in lithium response","volume":"19","author":"Pisanu","year":"2018","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1399-5618.2009.00667.x","article-title":"Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBalpha gene, a critical component of the circadian clock system","volume":"11","author":"Severino","year":"2009","journal-title":"Bipolar Disord."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s13105-018-0629-x","article-title":"Regulatory roles of miR-155 and let-7b on the expression of inflammation-related genes in THP-1 cells: Effects of fatty acids","volume":"74","author":"Samblas","year":"2018","journal-title":"J. Physiol. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1073\/pnas.0811073106","article-title":"MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells","volume":"106","author":"Ceppi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.euroneuro.2015.05.006","article-title":"Transcription factor SP4 phosphorylation is altered in the postmortem cerebellum of bipolar disorder and schizophrenia subjects","volume":"25","author":"Pinacho","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pinacho, R., Saia, G., Fuste, M., Melendez-Perez, I., Villalta-Gil, V., Haro, J.M., Gill, G., and Ramos, B. (2015). Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125115"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jad.2015.05.037","article-title":"Cellular models to study bipolar disorder: A systematic review","volume":"184","author":"Viswanath","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1001\/archpsyc.1978.01770300115013","article-title":"Research diagnostic criteria: Rationale and reliability","volume":"35","author":"Spitzer","year":"1978","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1001\/archpsyc.1978.01770310043002","article-title":"A diagnostic interview: The schedule for affective disorders and schizophrenia","volume":"35","author":"Endicott","year":"1978","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"942","DOI":"10.4088\/JCP.v63n1013","article-title":"Is response to prophylactic lithium a familial trait?","volume":"63","author":"Grof","year":"2002","journal-title":"J. Clin. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Manchia, M., Adli, M., Akula, N., Ardau, R., Aubry, J.M., Backlund, L., Banzato, C.E., Baune, B.T., Bellivier, F., and Bengesser, S. (2013). Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065636"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/BF00279094","article-title":"A routine method for the establishment of permanent growing lymphoblastoid cell lines","volume":"73","author":"Neitzel","year":"1986","journal-title":"Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_55","unstructured":"R Core-Team (2018). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Smyth, G.K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol., 3.","DOI":"10.2202\/1544-6115.1027"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vila-Casadesus, M., Gironella, M., and Lozano, J.J. (2016). MiRComb: An R Package to Analyse miRNA-mRNA Interactions. Examples across Five Digestive Cancers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151127"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.jbi.2011.05.002","article-title":"miRWalk--database: Prediction of possible miRNA binding sites by \"walking\" the genes of three genomes","volume":"44","author":"Dweep","year":"2011","journal-title":"J. Biomed. Inf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/6040\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:54Z","timestamp":1760189934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/6040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,30]]},"references-count":59,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ijms20236040"],"URL":"https:\/\/doi.org\/10.3390\/ijms20236040","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,30]]}}}