{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:12:02Z","timestamp":1779343922990,"version":"3.51.4"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"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>Background<\/jats:title>\n                    <jats:p>Uterine corpus endometrial carcinoma (UCEC) has significant inherent resistance to immunotherapy. The tumor microenvironment (TME) in UCEC is characterized by limited infiltration of T cells, which has been shown to be the cause of this resistance. Recent studies have indicated that dysregulation of splicing may be involved in tumor progression and immune evasion. However, the biological mechanisms underlying this phenomenon have not been fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the study, genome-wide association studies (GWAS), splicing quantitative trait loci (sQTL), and expression quantitative trait loci (eQTL) were used for prioritizing candidate targets for complex traits and small nuclear ribonucleoprotein polypeptide E (SNRPE) was screened for the further research. The prognostic value of SNRPE was evaluated in the TCGA-UCEC cohort and validated using an independent cohort of clinical UCEC patient specimens. Its functional role was validated through\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays and a doxycycline (Dox)-inducible xenograft model. Mechanistically, RNA sequencing (RNA-seq) was integrated with computational motif prediction and protein domain architecture analysis to identify aberrant alternative splicing (AS) events and assess their potential structural impacts. These findings were further validated via isoform-specific quantitative PCR. Concurrently, its immunomodulatory function was decoded using single-cell RNA sequencing (scRNA-seq) and experimentally validated via human peripheral blood mononuclear cells (PBMCs) co-culture assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified SNRPE as a driven oncogene, strongly connected to bad survival outcomes in people with UCEC. Knocking down SNRPE dramatically suppressed tumor progression both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Mechanistically, SNRPE played a critical role in maintaining accurate splicing of dual-function hub genes (PAK1, SOS1, PIK3CB, IL17RC). Depletion of SNRPE leaded to the skipping of specific exons and alterations in protein structure, resulting in the concurrent disruption of both intrinsic oncogenic signaling pathways and tumor immune surveillance mechanisms. Meanwhile, scRNA-seq analysis unveiled that SNRPE induces an immune evasion phenotype, characterized by a specific reduction in the expression of the major histocompatibility complex class I (MHC-I) antigen presentation system and an increase of immunosuppressive midkine (MDK) signaling. Co-culture experiments confirmed that silencing SNRPE significantly restores T cell-mediated cytotoxicity and reverses the expression of exhaustion markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By remodeling the global splicing network, SNRPE concurrently sustained intrinsic malignant progression and extrinsic immune suppression in UCEC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1827474","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:43:45Z","timestamp":1779342225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative multi-omics analysis identifies SNRPE as a key driver gene in uterine corpus endometrial carcinoma: promoting tumor progression, and mediating immune 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