{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:07:05Z","timestamp":1789020425084,"version":"build-2803163510"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioma is a molecularly heterogeneous tumor of the central nervous system with variable clinical behavior, immune contexture, and therapeutic response. Palmitoylation is a reversible lipid modification that regulates membrane localization, synaptic signaling, inflammatory pathways, and oncogenic signaling; however, the prognostic and functional relevance of palmitoylation-related long non-coding RNAs (PRlncRNAs) in glioma remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic and clinical data for 429 glioma patients were obtained from TCGA. Thirty palmitoylation-related genes were used to identify PRlncRNAs through co-expression analysis. A prognostic signature was constructed using univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression. The model was evaluated by Kaplan-Meier analysis, ROC curves, time-dependent ROC analysis, Cox regression, C-index analysis, nomogram modeling, calibration curves, and an institutional clinical cohort of 46 paired glioma and adjacent tissues. Functional enrichment, immune deconvolution, tumor microenvironment scoring, TIDE-based immunotherapy prediction, TMB\/MSI analysis, and pRRophetic-based drug-sensitivity analysis were performed. U87 and U251 glioma cells, LYRM4-AS1 knockdown,\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays, and nude-mouse xenografts were used for biological validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A six-PRlncRNA signature consisting of POLR2J4, LYRM4-AS1, BX640514.2, AL592295.6, AL390755.1, and AC018730.1 stratified glioma patients into high- and low-risk groups with significantly different overall survival. The risk score remained an independent prognostic factor and showed strong predictive performance for 1-, 3-, and 5-year survival. Risk-associated genes were enriched in extracellular matrix organization, leukocyte-mediated immunity, neuroactive ligand-receptor interaction, MAPK signaling, cytokine-receptor interaction, cell-cycle programs, and ECM-receptor interaction. High-risk tumors displayed increased stromal, immune, and ESTIMATE scores, higher expression of multiple immune checkpoint genes, higher TIDE scores, and elevated TMB\/MSI levels. Clinical validation confirmed differential expression of the six PRlncRNAs and the prognostic value of the risk score. Functionally, LYRM4-AS1 knockdown inhibited glioma cell proliferation, EdU incorporation, migration, invasion, and colony formation, while suppressing xenograft growth, increasing TUNEL-positive apoptotic cells, and reducing Ki-67, CD31, and MMP9 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies a palmitoylation-related lncRNA signature that integrates molecular signaling, immune remodeling, and prognosis in glioma. LYRM4-AS1 acts as a functional driver of glioma progression and may represent a candidate biomarker and therapeutic target at the crossroads of neural tumorigenesis and immune-microenvironmental regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1901839","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:33:29Z","timestamp":1789018409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Palmitoylation-related lncRNAs link molecular signaling, immune remodeling, and tumor progression in glioma: prognostic modeling and functional validation of LYRM4-AS1"],"prefix":"10.3389","volume":"19","author":[{"given":"Juan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei University of Medicine, Shiyan","place":["Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Encephalopathy, The Second Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fourth Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: Digitally portraying the tissue cellular heterogeneity landscape.","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression.","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3965","DOI":"10.1158\/0008-5472.CAN-16-2634","article-title":"Long noncoding RNA and cancer: A new paradigm.","volume":"77","author":"Bhan","year":"2017","journal-title":"Cancer Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The somatic genomic landscape of glioblastoma.","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments.","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. 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