{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:11:49Z","timestamp":1783768309186,"version":"3.55.0"},"reference-count":95,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (Conahcyt)","award":["CBF2023-2024-4056"],"award-info":[{"award-number":["CBF2023-2024-4056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20\u201340% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis.<\/jats:p>","DOI":"10.3390\/ijms251910325","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"10325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MicroRNAs in Lung Cancer Brain Metastasis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-4655","authenticated-orcid":false,"given":"Israel","family":"Mart\u00ednez-Espinosa","sequence":"first","affiliation":[{"name":"Department of Molecular Biomedicine and Translational Research, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, 14080 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4252-2638","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Serrato","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine and Translational Research, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, 14080 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6298-0073","authenticated-orcid":false,"given":"Blanca","family":"Ortiz-Quintero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedicine and Translational Research, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, 14080 Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1093\/neuonc\/nox077","article-title":"Incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy: A population-based study","volume":"19","author":"Cagney","year":"2017","journal-title":"Neuro. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11060-004-8093-6","article-title":"Brain metastases: Epidemiology and pathophysiology","volume":"75","author":"Gavrilovic","year":"2005","journal-title":"J. Neurooncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1002\/cncr.10541","article-title":"Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma","volume":"94","author":"Schouten","year":"2002","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e373","DOI":"10.1016\/j.cllc.2018.01.007","article-title":"Non-small-cell Lung Cancer With Brain Metastasis at Presentation","volume":"19","author":"Waqar","year":"2018","journal-title":"Clin. Lung Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11912-011-0203-y","article-title":"Epidemiology of brain metastases","volume":"14","author":"Nayak","year":"2012","journal-title":"Curr. Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5038","DOI":"10.1002\/cncr.25254","article-title":"Factors associated with the development of brain metastases: Analysis of 975 patients with early stage nonsmall cell lung cancer","volume":"116","author":"Hubbs","year":"2010","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1200\/JCO.2005.04.123","article-title":"High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation","volume":"23","author":"Mamon","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.lungcan.2018.12.027","article-title":"Incidence of brain metastasis in lung adenocarcinoma at initial diagnosis on the basis of stage and genetic alterations","volume":"129","author":"Yang","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/neuonc\/nou099","article-title":"Incidence of brain metastasis at initial presentation of lung cancer","volume":"17","author":"Villano","year":"2015","journal-title":"Neuro. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.jtho.2023.06.017","article-title":"Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis","volume":"18","author":"Gillespie","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10131","DOI":"10.2147\/IJGM.S342009","article-title":"Brain Metastasis in Patients with Small Cell Lung Cancer","volume":"14","author":"Li","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/(SICI)1097-0142(19961015)78:8<1781::AID-CNCR19>3.0.CO;2-U","article-title":"Brain metastases. Histology, multiplicity, surgery, and survival","volume":"78","author":"Nussbaum","year":"1996","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e300","DOI":"10.3747\/co.20.1481","article-title":"Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases","volume":"20","author":"Ali","year":"2013","journal-title":"Curr. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1200\/JCO.20.01255","article-title":"Survival in Patients With Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient","volume":"38","author":"Sperduto","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1001\/jamaoncol.2016.3834","article-title":"Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung-molGPA)","volume":"3","author":"Sperduto","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of MicroRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/s41576-023-00611-y","article-title":"microRNAs in action: Biogenesis, function and regulation","volume":"24","author":"Shang","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41572-018-0055-y","article-title":"Brain metastases","volume":"5","author":"Achrol","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ccr.2011.09.009","article-title":"Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis","volume":"20","author":"Labelle","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10409238.2013.838205","article-title":"Transcriptional regulation by hypoxia inducible factors","volume":"49","author":"Dengler","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev-cellbio-100617-062608","article-title":"Development and Cell Biology of the Blood-Brain Barrier","volume":"35","author":"Langen","year":"2019","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, maintenance and disruption of the blood-brain barrier","volume":"19","author":"Obermeier","year":"2013","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1158\/1535-7163.MCT-23-0416","article-title":"A Review of Recent Advances in the Molecular Mechanisms Underlying Brain Metastasis in Lung Cancer","volume":"23","author":"Guan","year":"2024","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Daneman, R., and Prat, A. (2015). The blood-brain barrier. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a020412"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2015.01.002","article-title":"Anatomy and physiology of the blood-brain barrier","volume":"38","author":"Serlin","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1038\/s41467-022-34412-4","article-title":"Reactive astrocytes transduce inflammation in a blood-brain barrier model through a TNF-STAT3 signaling axis and secretion of alpha 1-antichymotrypsin","volume":"13","author":"Kim","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1093\/neuonc\/noaa028","article-title":"ALCAM contributes to brain metastasis formation in non-small-cell lung cancer through interaction with the vascular endothelium","volume":"22","author":"Munsterberg","year":"2020","journal-title":"Neuro. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1158\/0008-5472.CAN-03-3235","article-title":"Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis","volume":"64","author":"Shintani","year":"2004","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/neuonc\/nov248","article-title":"TNF-\u03b1 enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis","volume":"18","author":"Jassam","year":"2016","journal-title":"Neuro. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s11060-019-03188-x","article-title":"Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood-brain-barrier: In vitro investigation of CD15 and CD15s in lung-to-brain metastasis","volume":"143","author":"Jassam","year":"2019","journal-title":"J. Neurooncol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tiwary, S., Morales, J.E., Kwiatkowski, S.C., Lang, F.F., Rao, G., and McCarty, J.H. (2018). Metastatic Brain Tumors Disrupt the Blood-Brain Barrier and Alter Lipid Metabolism by Inhibiting Expression of the Endothelial Cell Fatty Acid Transporter Mfsd2a. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-26636-6"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/cns.12764","article-title":"Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis","volume":"23","author":"Ma","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/mc.23161","article-title":"Adenosine A2A receptor activation reduces brain metastasis via SDF-1\/CXCR4 axis and protecting blood-brain barrier","volume":"59","author":"Chen","year":"2020","journal-title":"Mol. Carcinog."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.actbio.2019.04.053","article-title":"AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model","volume":"91","author":"Liu","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1158\/0008-5472.CAN-22-3964","article-title":"Active Remodeling of Capillary Endothelium via Cancer Cell-Derived MMP9 Promotes Metastatic Brain Colonization","volume":"83","author":"Karreman","year":"2023","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1038\/onc.2012.313","article-title":"Elevated PLGF contributes to small-cell lung cancer brain metastasis","volume":"32","author":"Li","year":"2013","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11439","DOI":"10.3390\/ijms160511439","article-title":"Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2","volume":"16","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.biocel.2015.06.019","article-title":"Brain microvascular endothelium induced-annexin A1 secretion contributes to small cell lung cancer brain metastasis","volume":"66","author":"Liu","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.trecan.2018.01.003","article-title":"The Evolving Landscape of Brain Metastasis","volume":"4","author":"Valiente","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nm.2072","article-title":"Real-time imaging reveals the single steps of brain metastasis formation","volume":"16","author":"Kienast","year":"2010","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chen, J., Hu, C., Yang, H., Wang, L., Chu, X., Yu, X., Zhang, S., Li, X., Zhao, C., and Cheng, L. (2024). PMS2 amplification contributes brain metastasis from lung cancer. Biol. Proced. Online, 26.","DOI":"10.1186\/s12575-024-00238-1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/s12276-024-01255-6","article-title":"Dissecting the MUC5AC\/ANXA2 signaling axis: Implications for brain metastasis in lung adenocarcinoma","volume":"56","author":"Chaudhary","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101533","DOI":"10.1016\/j.xcrm.2024.101533","article-title":"Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity","volume":"5","author":"Wang","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.cell.2014.01.040","article-title":"Serpins promote cancer cell survival and vascular co-option in brain metastasis","volume":"156","author":"Valiente","year":"2014","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215713","DOI":"10.1016\/j.canlet.2022.215713","article-title":"Metabolism in the progression and metastasis of brain tumors","volume":"539","author":"Tyagi","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41568-019-0220-y","article-title":"Brain metastasis","volume":"20","author":"Boire","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_48","first-page":"v121","article-title":"The microenvironment of brain metastases from solid tumors","volume":"3","author":"Srinivasan","year":"2021","journal-title":"Neurooncol. Adv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41568-020-00320-2","article-title":"The metabolism of cancer cells during metastasis","volume":"21","author":"Bergers","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1158\/0008-5472.CAN-14-2268","article-title":"Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain","volume":"75","author":"Chen","year":"2015","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1158\/0008-5472.CAN-06-3137","article-title":"Adaptation of energy metabolism in breast cancer brain metastases","volume":"67","author":"Chen","year":"2007","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.1038\/s41388-019-0893-4","article-title":"FABP7 is a key metabolic regulator in HER2+ breast cancer brain metastasis","volume":"38","author":"Cordero","year":"2019","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ortiz-Quintero, B. (2020). Extracellular MicroRNAs as Intercellular Mediators and Noninvasive Biomarkers of Cancer. Cancers, 12.","DOI":"10.3390\/cancers12113455"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.cell.2009.01.035","article-title":"Origins and Mechanisms of miRNAs and siRNAs","volume":"136","author":"Carthew","year":"2009","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1038\/sj.emboj.7600385","article-title":"MicroRNA genes are transcribed by RNA polymerase II","volume":"23","author":"Lee","year":"2004","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1261\/rna.5167604","article-title":"Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs","volume":"10","author":"Bohnsack","year":"2004","journal-title":"RNA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature03049","article-title":"Processing of primary microRNAs by the Microprocessor complex","volume":"432","author":"Denli","year":"2004","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.molcel.2014.11.030","article-title":"Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis","volume":"57","author":"Wilson","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.molcel.2012.05.012","article-title":"MicroRNA factory: RISC assembly from precursor microRNAs","volume":"46","author":"Kim","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target recognition and regulatory functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1126\/science.1258040","article-title":"Structural basis for microRNA targeting","volume":"346","author":"Schirle","year":"2014","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.molcel.2014.03.036","article-title":"Structural and biochemical insights to the role of the CCR4-NOT complex and DDX6 ATPase in microRNA repression","volume":"54","author":"Mathys","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1093\/nar\/gkt1265","article-title":"Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated silencing","volume":"42","author":"Kamenska","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41580-020-0251-y","article-title":"RNA delivery by extracellular vesicles in mammalian cells and its applications","volume":"21","author":"Breyne","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.semcancer.2019.08.017","article-title":"Extracellular vesicles in cancer nanomedicine","volume":"69","author":"Tarasov","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Souza, V.G.P., de Araujo, R.P., Santesso, M.R., Seneda, A.L., Minutentag, I.W., Felix, T.F., Hamamoto Filho, P.T., Pewarchuk, M.E., Brockley, L.J., and Marchi, F.A. (2023). Advances in the Molecular Landscape of Lung Cancer Brain Metastasis. Cancers, 15.","DOI":"10.3390\/cancers15030722"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11060-023-04541-x","article-title":"The role of microRNAs in brain metastasis","volume":"166","author":"Hudson","year":"2024","journal-title":"J. Neurooncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Siegl, F., Vecera, M., Roskova, I., Smrcka, M., Jancalek, R., Kazda, T., Slaby, O., and Sana, J. (2022). The Significance of MicroRNAs in the Molecular Pathology of Brain Metastases. Cancers, 14.","DOI":"10.3390\/cancers14143386"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2147\/OTT.S116619","article-title":"The role of microRNA-21 in predicting brain metastases from non-small cell lung cancer","volume":"10","author":"Dong","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s12094-015-1347-2","article-title":"miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers","volume":"18","author":"Remon","year":"2016","journal-title":"Clin. Transl. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.prp.2017.06.012","article-title":"Down-regulated microRNA-375 expression as a predictive biomarker in non-small cell lung cancer brain metastasis and its prognostic significance","volume":"213","author":"Chen","year":"2017","journal-title":"Pathol. Res. Pract."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Tsakonas, G., Koulouris, A., Kazmierczak, D., Botling, J., Ortiz-Villalon, C., Nord, H., Lindskog, M., Sandelin, M., Micke, P., and Hydbring, P. (2022). Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010193"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.tranon.2017.12.002","article-title":"Machine Learning Based Prediction of Brain Metastasis of Patients with IIIA-N2 Lung Adenocarcinoma by a Three-miRNA Signature","volume":"11","author":"Zhao","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Gayosso-Gomez, L.V., and Ortiz-Quintero, B. (2021). Circulating MicroRNAs in Blood and Other Body Fluids as Biomarkers for Diagnosis, Prognosis, and Therapy Response in Lung Cancer. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030421"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6734","DOI":"10.18632\/aging.102201","article-title":"MicroRNA-330-3p promotes brain metastasis and epithelial-mesenchymal transition via GRIA3 in non-small cell lung cancer","volume":"11","author":"Wei","year":"2019","journal-title":"Aging"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.2147\/OTT.S301412","article-title":"Irradiation-Induced Activated Microglia Affect Brain Metastatic Colonization of NSCLC Cells via miR-9\/CDH1 Axis","volume":"14","author":"Jin","year":"2021","journal-title":"OncoTargets Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"27461","DOI":"10.18632\/oncotarget.4742","article-title":"STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation","volume":"6","author":"Singh","year":"2015","journal-title":"Oncotarget"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1002\/ijc.25939","article-title":"MicroRNA-328 is associated with (non-small) cell lung cancer (NSCLC) brain metastasis and mediates NSCLC migration","volume":"129","author":"Arora","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1007\/s12032-011-0083-x","article-title":"MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis","volume":"29","author":"Chen","year":"2012","journal-title":"Med. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1186\/s12935-021-02197-z","article-title":"MicroRNA-550a-3-5p controls the brain metastasis of lung cancer by directly targeting YAP1","volume":"21","author":"Wei","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Choi, K.H., Shin, C.H., Lee, W.J., Ji, H., and Kim, H.H. (2019). Dual-strand tumor suppressor miR-193b-3p and -5p inhibit malignant phenotypes of lung cancer by suppressing their common targets. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190634"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jiang, C., Zhao, H., Yang, B., Sun, Z., Li, X., and Hu, X. (2020). lnc-REG3G-3-1\/miR-215-3p Promotes Brain Metastasis of Lung Adenocarcinoma by Regulating Leptin and SLC2A5. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01344"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4274\/balkanmedj.galenos.2020.2019.9.91","article-title":"Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53\/KAI1 Signaling","volume":"37","author":"Jiang","year":"2020","journal-title":"Balk. Med. J."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Subramani, A., Alsidawi, S., Jagannathan, S., Sumita, K., Sasaki, A.T., Aronow, B., Warnick, R.E., Lawler, S., and Driscoll, J.J. (2013). The brain microenvironment negatively regulates miRNA-768-3p to promote K-ras expression and lung cancer metastasis. Sci. Rep., 3.","DOI":"10.1038\/srep02392"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/s41419-022-05062-7","article-title":"miR-596-3p suppresses brain metastasis of non-small cell lung cancer by modulating YAP1 and IL-8","volume":"13","author":"Li","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"20434","DOI":"10.18632\/oncotarget.3886","article-title":"Overexpression of microRNA-95-3p suppresses brain metastasis of lung adenocarcinoma through downregulation of cyclin D1","volume":"6","author":"Hwang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"35183","DOI":"10.18632\/oncotarget.5930","article-title":"Epigenetic silencing of miR-145-5p contributes to brain metastasis","volume":"6","author":"Donzelli","year":"2015","journal-title":"Oncotarget"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41419-021-04004-z","article-title":"TGF-\u03b21-mediated exosomal lnc-MMP2-2 increases blood-brain barrier permeability via the miRNA-1207-5p\/EPB41L5 axis to promote non-small cell lung cancer brain metastasis","volume":"12","author":"Wu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s13046-018-0882-4","article-title":"miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2)","volume":"37","author":"He","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/s41419-018-0955-5","article-title":"MiR-423-5p in brain metastasis: Potential role in diagnostics and molecular biology","volume":"9","author":"Sun","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1038\/s41467-017-00983-w","article-title":"TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p","volume":"8","author":"Berrout","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.tig.2022.02.006","article-title":"Emerging concepts of miRNA therapeutics: From cells to clinic","volume":"38","author":"Diener","year":"2022","journal-title":"Trends Genet."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Seyhan, A.A. (2024). Trials and Tribulations of MicroRNA Therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031469"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jare.2020.08.012","article-title":"Therapeutic advances of miRNAs: A preclinical and clinical update","volume":"28","author":"Chakraborty","year":"2021","journal-title":"J. Adv. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10325\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:03:09Z","timestamp":1760112189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,25]]},"references-count":95,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910325"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910325","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,25]]}}}