{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:14:52Z","timestamp":1790144092748,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>LINC00887 plays critical roles in tumor biology, from oncogenesis to metastasis and drug resistance, while the specific mechanism in ccRCC remains unclear. We analyzed the expression profiles of LINC00887 and UPF1 and assessed their correlation with glycolytic activity and M2 macrophage infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we performed scRNA-seq to identify distinct UPF1 expression profiles and found significant pathways. A suite of assay kits was utilized to evaluate glycolytic metabolism. Glycolytic gene expression at the mRNA and protein levels was quantified via qRT-PCR and immunoblot. Macrophage polarization and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were analyzed via flow cytometry, and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell cytotoxicity was quantified with an LDH release assay. Orthotopic tumor models were built for validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that highly expressed LINC00887 induced M2 macrophage polarization by activating aerobic glycolysis and promoting lactate buildup. Mechanistically, suppression of UPF1 expression promoted malignant progression of ccRCC. Additionally, UPF1 was found to be negatively correlated with aerobic glycolysis, repressing glycolytic activity and M2 macrophage polarization while bolstering the tumor-killing potential of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In summary, LINC00887, through the inhibition of UPF1, escalates glycolytic activity in ccRCC and induces M2 macrophage polarization, impairing the effectiveness of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in combating the tumor.\n                    <\/jats:p>\n                  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