2024
Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment
Martinez-Terroba E, Plasek-Hegde L, Chiotakakos I, Li V, de Miguel F, Robles-Oteiza C, Tyagi A, Politi K, Zamudio J, Dimitrova N. Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment. Science Immunology 2024, 9: eadh5462. PMID: 38875320, DOI: 10.1126/sciimmunol.adh5462.Peer-Reviewed Original ResearchConceptsTumor microenvironmentLung adenocarcinomaMetastatic diseasePromoting metastatic diseaseGlobal chromatin accessibilityMetastasis-associated lung adenocarcinoma transcript 1Overexpression of MALAT1Lung adenocarcinoma transcript 1Lung adenocarcinoma metastasisCCL2 blockadeInflammatory reprogrammingEnhanced cell mobilityMacrophage depletionMechanism of actionTumor typesTumor progressionMouse modelCell mobilizationTumorLong noncoding RNAsParacrine secretionMetastasisCell linesTranscript 1Microenvironment
2021
The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs
Tesfaye E, Martinez-Terroba E, Bendor J, Winkler L, Olivero C, Chen K, Feldser DM, Zamudio JR, Dimitrova N. The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025539118. PMID: 34326251, PMCID: PMC8346867, DOI: 10.1073/pnas.2025539118.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorCell ProliferationCellular SenescenceDNA DamageE2F Transcription FactorsGene Expression Regulation, NeoplasticGenome-Wide Association StudyMiceNeoplasmsProto-Oncogene Proteins c-mycRNA, Long NoncodingSignal TransductionStress, PhysiologicalTumor Suppressor Protein p53ConceptsOncogenic contextPermanent cell cycle arrestP53-induced lncRNAsP53 transcriptional responseMYC target genesTumor suppressor mechanismRepression of E2FP53-binding siteP53-dependent senescenceTumor-type specificCell cycle arrestTranscriptional responseProliferative arrestTarget genesMurine cancer cell linesTranscriptional signatureRegulatory axisTumor typesCycle arrestP53 functionDistinct tumor typesFunctional investigationDownstream mediatorP53 pathwayCancer cell lines
2020
Identification and characterization of functional long noncoding RNAs in cancer
Olivero CE, Dimitrova N. Identification and characterization of functional long noncoding RNAs in cancer. The FASEB Journal 2020, 34: 15630-15646. PMID: 33058262, PMCID: PMC7756267, DOI: 10.1096/fj.202001951r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansNeoplasmsRNA, Long Noncodingp53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis
Olivero CE, Martínez-Terroba E, Zimmer J, Liao C, Tesfaye E, Hooshdaran N, Schofield JA, Bendor J, Fang D, Simon MD, Zamudio JR, Dimitrova N. p53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis. Molecular Cell 2020, 77: 761-774.e8. PMID: 31973890, PMCID: PMC7184554, DOI: 10.1016/j.molcel.2019.12.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell LineCell ProliferationCells, CulturedChromatinEnhancer Elements, GeneticGene Expression RegulationHumansLung NeoplasmsMiceMice, Inbred C57BLPromoter Regions, GeneticProto-Oncogene MasProto-Oncogene Proteins c-mycRNA, Long NoncodingStress, PhysiologicalTumor Suppressor Protein p53ConceptsMYC transcriptional networkLong noncoding RNA PVT1Cellular proliferationTumor suppressor p53Chromatin organizationTranscriptional networksTarget genesMYC transcriptionTranscriptional activityKb downstreamMYC levelsOncogenic signalingSuppressor p53Suppress tumorigenesisDNA damageRNA PVT1Autochthonous mouse modelMYCTranscriptionP53Anti-proliferative activityTumor progressionTumor growthLung cancerMouse model
2014
LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint
Dimitrova N, Zamudio JR, Jong RM, Soukup D, Resnick R, Sarma K, Ward AJ, Raj A, Lee JT, Sharp PA, Jacks T. LincRNA-p21 Activates p21 In cis to Promote Polycomb Target Gene Expression and to Enforce the G1/S Checkpoint. Molecular Cell 2014, 54: 777-790. PMID: 24857549, PMCID: PMC4103188, DOI: 10.1016/j.molcel.2014.04.025.Peer-Reviewed Original ResearchConceptsG1/S checkpointGene expressionS checkpointPolycomb target genesGlobal gene expressionP53 transcriptional networkTarget gene expressionTumor suppressor pathwayConditional knockout mouse modelP53 tumor suppressor pathwayChromatin stateTranscriptional networksKnockout mouse modelNeighboring genesMRNA translationProtein stabilityTarget genesP21 transcriptionSuppressor pathwayAdditional phenotypesGenesP21 levelsLincRNA-p21P21 expressionCoactivator