{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:38:04Z","timestamp":1768509484384,"version":"3.49.0"},"posted":{"date-parts":[[2023,11,15]]},"group-title":"Cancer Biology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:bold>\n                    Obesity-linked fatty liver is a significant risk factor for hepatocellular carcinoma (HCC)\n                    <jats:sup>1,2<\/jats:sup>\n                    ; however, the molecular mechanisms underlying the transition from non-alcoholic fatty liver disease (NAFLD) to HCC remains unclear. The present study explores the role of the endoplasmic reticulum (ER)-associated protein NgBR, an essential component of the cis-prenyltransferases (cis-PTase) enzyme\n                    <jats:sup>3<\/jats:sup>\n                    , in chronic liver disease. Here we show that genetic depletion of NgBR in hepatocytes of mice (N-LKO) intensifies triacylglycerol (TAG) accumulation, inflammatory responses, ER\/oxidative stress, and liver fibrosis, ultimately resulting in HCC development with 100% penetrance after four months on a high-fat diet. Comprehensive genomic and single cell transcriptomic atlas from affected livers provides a detailed molecular analysis of the transition from liver pathophysiology to HCC development. Importantly, pharmacological inhibition of diacylglycerol acyltransferase-2 (DGAT2), a key enzyme in hepatic TAG synthesis, abrogates diet-induced liver damage and HCC burden in N-LKO mice. Overall, our findings establish NgBR\/cis-PTase as a critical suppressor of NAFLD-HCC conversion and suggests that DGAT2 inhibition may serve as a promising therapeutic approach to delay HCC formation in patients with advanced non-alcoholic steatohepatitis (NASH).\n                  <\/jats:bold>\n                <\/jats:p>","DOI":"10.1101\/2023.11.13.566870","type":"posted-content","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T14:40:15Z","timestamp":1700059215000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of cis-PTase function in the liver promotes a highly penetrant form of fatty liver disease that rapidly transitions to hepatocellular carcinoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4474-1367","authenticated-orcid":false,"given":"Abhishek 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