{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:55:14Z","timestamp":1791467714881,"version":"4.3.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":90,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Liaoning Province Science and Technology Plan Joint Project","award":["2024-MSLH-535"],"award-info":[{"award-number":["2024-MSLH-535"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Oncol."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Renal cell carcinoma (RCC) is a common kidney cancer, and clear cell RCC (ccRCC) represents the most common pathological type. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells are the most primary killing cells in tumor microenvironment (TME). Ring finger protein 149 (RNF149) played tumor-promoting roles in several tumors, and its roles in ccRCC remained unclear. This study aims to investigate the role of RNF149 in ccRCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The expression of RNF149 in clinical ccRCC specimens was determined with western blot and immunohistochemistry staining, and the overexpression or knockdown of RNF149 in ccRCC cells were realized via lentivirus infection. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were co-cultured with tumor cells, and the exhaustion-associated markers were assessed with ELISA and flow cytometry. Xenograft experiment was performed in wild type and nude mice to measure the CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration in tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNF149 was upregulated in ccRCC specimens, compared with the para-carcinoma normal kidney tissues, and its expression was associated with tumor size and TNM stage. Gain- and loss-of-function experiments revealed that RNF149 promoted the colony formation, and inhibited apoptosis of ccRCC cells, in the presence of co-culture with CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. The RNF149-overexpressed ccRCC induced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells an exhaustion-associated phenotype, evidenced by the decreased production of interferon-\u03b3, tumor necrosis factor-\u03b1, granzyme B and perforin-1, and the expression of PD-1, lymphocyte activating 3 (LAG3), T-cell immunoglobulin and mucin domain 3 (TIM3) and T cell immunoreceptor with Ig and ITIM domain (TIGIT). Xenograft experiments displayed that knockdown of RNF149 delayed tumorigenesis of ccRCC cells in wild type mice, and accelerated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration in tumors. As an E3 ligase, RNF149 bound to RNA binding motif protein 25 (RBM25), and mediated its ubiquitination and degradation. RNF149 facilitated programmed cell death 1 ligand 1 (PD-L1) expression by destabilizing RBM25 and promoting MYC transcription activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      RNF149 promoted ccRCC growth in vivo and in vitro, and induced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells an exhaustion-associated phenotype in TME by catalyzing RBM25 ubiquitination and activating PD-L1 transcription. These findings may provide novel insights for clinical immunotherapy of ccRCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13402-026-01262-x","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:46:43Z","timestamp":1783698403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RNF149\/RBM25\/MYC\/PD-L1 axis promotes CD8+ T cell dysfunction in microenvironment of clear cell renal cell carcinoma"],"prefix":"10.1007","volume":"49","author":[{"given":"Xuefei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingming","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhua","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"issue":"3","key":"1262_CR1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1097\/00000478-200203000-00001","volume":"26","author":"MB Amin","year":"2002","unstructured":"M.B. 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