{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:45:22Z","timestamp":1791827122957,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical & Translational Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Current therapeutic outcomes for advanced colorectal cancer (CRC) remain suboptimal, and chemotherapy\u2010based regimens continue to be the mainstay of treatment. Circular RNAs (circRNAs) can serve as templates for translating short peptides or proteins, and the resulting products actively regulate malignant tumour progression, making them attractive therapeutic targets.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We identified the novel protein PVT1\u2010104aa translated from circPVT1, which is generated by back\u2010splicing of the non\u2010coding\n PVT<\/jats:italic>\n 1 gene. Its expression and clinical significance were examined in CRC clinical specimens and cell lines. Proliferation, metastasis, and tumour growth were assessed by CCK\u20108, colony formation, transwell, wound healing, and xenograft syngeneic tumour models. Mechanistic studies were performed by immunoprecipitation, ubiquitination assays, and protein half\u2010life analysis. The relationship between PVT1\u2010104aa, c\u2010Myc, and PD\u2010L1 was evaluated by promoter reporter assays, ChIP\u2010qPCR, and immunohistochemistry. The therapeutic efficacy of combining PVT1\u2010104aa inhibition with anti\u2010PD\u2010L1 therapy was tested in vivo.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n PVT1\u2010104aa was significantly overexpressed in CRC and correlated with poor patient prognosis. Functionally, it drove tumour progression by promoting proliferation and metastasis. Mechanistically, PVT1\u2010104aa enhanced c\u2010Myc phosphorylation at Ser62, disrupted the c\u2010Myc\u2010FBW7 interaction, and thereby inhibited ubiquitin\u2010mediated degradation of c\u2010Myc, as shown by accelerated c\u2010Myc turnover upon PVT1\u2010104aa knockdown. In addition, PVT1\u2010104aa regulated PD\u2010L1 expression through c\u2010Myc. Combining anti\u2010PVT1\u2010104aa with anti\u2010PD\u2010L1 therapy suppressed CRC growth and increased CD4\n +<\/jats:sup>\n and CD8\n +<\/jats:sup>\n T cell infiltration in xenograft syngeneic tumour models and CRC tissues.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results uncover a pathogenic role of the PVT1\u2010originated molecular species PVT1\u2010104aa and suggest that targeting this pathway represents a promising therapeutic strategy for CRC treatment.<\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Circ\u2010PVT1 is upregulated in CRC patients and encoded a novel protein: PVT1\u2010104aa.<\/jats:p>\n <\/jats:list-item>\n \n PVT1\u2010104aa promotes CRC progression and predicts worse prognosis.<\/jats:p>\n <\/jats:list-item>\n \n PVT1\u2010104aa enhance Myc expression through inhibition of Myc ubiquitination.<\/jats:p>\n <\/jats:list-item>\n \n PVT1\u2010104aa regulate PD\u2010L1 expression of CRC cells and modulate T cells infiltration in vivo.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ctm2.70654","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:41:34Z","timestamp":1775716894000},"source":"Crossref","is-referenced-by-count":2,"title":["PVT1\u2010104aa derived from the 8q24 gene desert promotes colorectal cancer tumorigenesis"],"prefix":"10.1002","volume":"16","author":[{"given":"Maoguang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Fudan University Shanghai Cancer Center Shanghai China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingdian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital, Fudan University Shanghai 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