{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:07:00Z","timestamp":1780387620543,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304288"],"award-info":[{"award-number":["82304288"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303236"],"award-info":[{"award-number":["82303236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alternative splicing plays a crucial role in the development and progression of hepatocellular carcinoma (HCC), yet the underlying regulatory mechanisms and therapeutic potential remain largely unexplored. Here, we identified the RNA\u2010binding protein FMR1 autosomal homolog 1 (FXR1) as a key driver of HCC pathogenesis through the regulation of alternative splicing. FXR1 was highly expressed in HCC tissues, and its elevated expression was associated with a poor prognosis. Mechanistically, high FXR1 induced the retention of exon 6 in\n                    <jats:italic>mitogen\u2010activated protein kinase\u2010activated protein kinase 5<\/jats:italic>\n                    (\n                    <jats:italic>MK5<\/jats:italic>\n                    ), generating a long, kinase\u2010competent isoform (termed\n                    <jats:italic>MK5\u2010L<\/jats:italic>\n                    ). This isoform acted as an important oncogenic factor for HCC progression by phosphorylating GSK3\u03b2 and subsequently activating the Wnt\/\u03b2\u2010catenin pathway. Functional studies showed that the FXR1\/MK5\u2010L axis is critical for HCC cell proliferation and metastasis, both in\u00a0vivo and in\u00a0vitro. Importantly, therapeutic intervention using an FXR1\u2010targeting antisense oligonucleotide (ASO) effectively suppresses tumor progression and metastasis in preclinical models by shifting splicing toward the inactive\n                    <jats:italic>MK5\u2010S<\/jats:italic>\n                    isoform. Overall, our study unveils a novel splicing\u2010mediated oncogenic pathway and establishes FXR1 and its downstream target MK5\u2010L as promising prognostic biomarkers and therapeutic targets for HCC.\n                  <\/jats:p>","DOI":"10.1111\/cas.70371","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:59:30Z","timestamp":1775728770000},"page":"1580-1593","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>FXR1<\/scp>\n                    \u2010Directed Alternative Splicing of\n                    <scp>MK5<\/scp>\n                    Drives Hepatocellular Carcinoma Progression by Activating\n                    <scp>GSK3\u03b2<\/scp>\n                    Signaling"],"prefix":"10.1111","volume":"117","author":[{"given":"Yutong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University  Chongqing 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