{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:24Z","timestamp":1785405204485,"version":"3.56.0"},"reference-count":102,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"extramural","award":["K08NS119882"],"award-info":[{"award-number":["K08NS119882"]}]},{"name":"extramural","award":["L40HD102847"],"award-info":[{"award-number":["L40HD102847"]}]},{"name":"Children\u2019s National Research Institute"},{"id":[{"id":"https:\/\/ror.org\/02201aj62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy with limited treatment options and poor clinical outcomes. There is growing interest in using Zika virus as a treatment for GBM due to its selectivity in finding and killing rapidly proliferating neural cells. Several studies reproducibly show that Zika can effectively kill GBM cells. We sought to uncover the molecular mechanisms driving this cytotoxic effect by performing a meta-analysis of transcriptomic studies in which Zika virus was used to kill GBM cells. We integrated four datasets from studies on GBM and added neuroblastoma (NBM) studies as an outgroup comparator. Our analysis identified a shared molecular signature of the Zika-infected GBM cell. Interestingly, GBM cells killed by the Zika virus showed dysregulation of pathways commonly implicated in proliferation and metastasis, including TNF, NF-\u03baB, and p53 signaling. Using a hypothesis-free design, we found several long non-coding RNAs (lncRNAs) that were consistently dysregulated in Zika-infected GBMs, many of which have previously unrecognized roles in cancer cell death. Among this group, we validated four lncRNAs for a role in Zika-mediated oncolysis. We functionally tested MELTF-AS1, TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 in adult GBM cell lines using siRNA-mediated knockdown. Silencing of MELTF-AS1 augmented Zika-induced cell death, while knockdown of TIPARP-AS1, NR2F1-AS1, and SLC9A3-AS1 attenuated oncolysis, identifying lncRNAs whose modulation is associated with altered Zika-mediated cytotoxicity. These findings elucidate candidate mechanisms of Zika oncolysis in GBM cell lines, highlight novel lncRNA targets, and support further exploration of lncRNA modulation as a strategy to enhance oncolytic virotherapy for GBM and related malignancies.<\/jats:p>","DOI":"10.3390\/cells15121088","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:00:48Z","timestamp":1781535648000},"page":"1088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic Meta-Analysis and Functional Validation Identify Long Non-Coding RNAs as Modulators of Zika Virus-Mediated Oncolysis in Glioblastoma Multiforme Cell Lines"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4836-3310","authenticated-orcid":false,"given":"Shriya","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Neurology, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Division of Neurophysiology, Epilepsy, and Critical Care, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Centers for Precision Medicine and Genomics Research, Children\u2019s National Research and Innovation Campus, 7144 13th Pl NW, Suite 1247, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gerlein","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Division of Neurophysiology, Epilepsy, and Critical Care, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Centers for Precision Medicine and Genomics Research, Children\u2019s National Research and Innovation Campus, 7144 13th Pl NW, Suite 1247, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-1014","authenticated-orcid":false,"given":"Allison R.","family":"Horvath","sequence":"additional","affiliation":[{"name":"Centers for Precision Medicine and Genomics Research, Children\u2019s National Research and Innovation Campus, 7144 13th Pl NW, Suite 1247, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Henderson","sequence":"additional","affiliation":[{"name":"Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene I.","family":"Hwang","sequence":"additional","affiliation":[{"name":"Division of Oncology, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-7531","authenticated-orcid":false,"given":"Roger J.","family":"Packer","sequence":"additional","affiliation":[{"name":"Brain Tumor Institute, Children\u2019s National Hospital, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbo","family":"Shao","sequence":"additional","affiliation":[{"name":"Centers for Precision Medicine and Genomics Research, Children\u2019s National Research and Innovation Campus, 7144 13th Pl NW, Suite 1247, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-8144","authenticated-orcid":false,"given":"Youssef A.","family":"Kousa","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Division of Neurophysiology, Epilepsy, and Critical Care, Children\u2019s National Hospital, Washington, DC 20010, USA"},{"name":"Centers for Precision Medicine and Genomics Research, Children\u2019s National Research and Innovation Campus, 7144 13th Pl NW, Suite 1247, Washington, DC 20012, USA"},{"name":"Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-4241","authenticated-orcid":false,"given":"Tamer A.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction, University of California, Davis, CA 95616, USA"},{"name":"Department of Clinical Pathology, College of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 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