{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T18:48:23Z","timestamp":1782499703409,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014426","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000}}],"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 82171563, 82372902 and 82403370"],"award-info":[{"award-number":["No. 82171563, 82372902 and 82403370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["No. 2023JJ50243, 2025JJ70210"],"award-info":[{"award-number":["No. 2023JJ50243, 2025JJ70210"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hunan Provincial Health Commission Scientific Research Project Fund","award":["No. 20254138"],"award-info":[{"award-number":["No. 20254138"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The crosstalk between lactylation and autophagy within the hepatocellular carcinoma (HCC) microenvironment is a burgeoning field with profound implications. By integrating multi-omics data from public cohorts, we delineated two molecular subtypes of HCC with divergent clinical outcomes and established a lactylation-autophagy-related prognostic signature. This signature highlighted CLEC3B as a pivotal gene. Subsequent single-cell RNA sequencing and experimental validation unequivocally pinpointed liver sinusoidal endothelial cells (LSECs) as the principal cellular source of CLEC3B, which was significantly downregulated in HCC tissues. Functionally, conditioned media derived from CLEC3B-overexpressing LSECs potently inhibited HCC cell proliferation. Mechanistic investigations revealed that this tumor-suppressive effect was orchestrated through the concurrent suppression of autophagy and diminution of lactylation levels. Our findings position LSEC-secreted CLEC3B as a novel metabolic mediator in HCC, bridging two key pathways in tumor suppression, and endorse its clinical value both as a prognostic indicator and a promising therapeutic target.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1014426","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:55:44Z","timestamp":1782150944000},"page":"e1014426","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A lactylation- and autophagy-associated prognostic signature reveals LSEC-derived CLEC3B as a novel mediator of hepatocellular carcinoma 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