{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T19:42:19Z","timestamp":1772912539955,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University-Industry Collaboration Programme, the Innovation and Technology Commission, (Hong Kong)","award":["UIM367"],"award-info":[{"award-number":["UIM367"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) patients and are commonly associated with a poor prognosis. The tumor microenvironment (TME) is a complex milieu that plays a critical role in epigenetic alterations driving tumor development and metastatic progression. However, the impact of epigenetic alterations on metastatic ovarian cancer cells in the harsh peritoneal microenvironment remains incompletely understood. Here, we identified that miR-33b is frequently silenced by promoter hypermethylation in HGSOC cells derived from metastatic omental tumor tissues. Enforced expression of miR-33b abrogates the oncogenic properties of ovarian cancer cells cocultured in omental conditioned medium (OCM), which mimics the ascites microenvironment, and in vivo tumor growth. Of note, restoration of miR-33b inhibited OCM-upregulated de novo lipogenesis and fatty acid \u03b2-oxidation in ovarian cancer cells, indicating that miR-33b may play a novel tumor suppressor role in the lipid-mediated oncogenic properties of metastatic ovarian cancer cells found in the omentum. Mechanistic studies demonstrated that miR-33b directly targets transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing the activities of fatty acid synthase (FASN) and carnitine palmitoyltransferase 1A (CPT1A) in modulating lipid metabolic activities and simultaneously inhibiting the phosphorylation of NF-\u03baB signaling to govern the oncogenic behaviors of ovarian cancer cells. Thus, our data suggest that a lipid-rich microenvironment may cause epigenetic silencing of miR-33b, which negatively modulates ovarian cancer peritoneal metastases, at least in part, by suppressing TAK1\/FASN\/CPT1A\/NF-\u03baB signaling.<\/jats:p>","DOI":"10.3390\/cancers13194795","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T01:59:47Z","timestamp":1632707987000},"page":"4795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer by Modulating the TAK1\/FASN\/CPT1A\/NF-\u03baB Axis"],"prefix":"10.3390","volume":"13","author":[{"given":"Xueyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-1164","authenticated-orcid":false,"given":"Mingo M. H.","family":"Yung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5306-3457","authenticated-orcid":false,"given":"Rakesh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Centre for PanorOmic Sciences Proteomics and Metabolomics Core, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fushun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Tung","family":"Poon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai-Yip","family":"Lam","sequence":"additional","affiliation":[{"name":"Lee\u2019s Pharmaceutical (HK) Ltd., 1\/F Building 20E, Phase 3, Hong Kong Science Park, Shatin, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Li","sequence":"additional","affiliation":[{"name":"Lee\u2019s Pharmaceutical (HK) Ltd., 1\/F Building 20E, Phase 3, Hong Kong Science Park, Shatin, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hextan Y. S.","family":"Ngan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen K. L.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-3467","authenticated-orcid":false,"given":"David W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Hong, X., Chen, X., Hu, C., Lu, W., Xie, B., Zhong, L., Zhang, W., Cao, H., and Chen, B. (2021). Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux. 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