{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:43:13Z","timestamp":1767861793987,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA222274"],"award-info":[{"award-number":["1R01CA222274"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>AKT\u2010mTORC1 (mammalian target of rapamycin complex 1) signaling pathway plays a critical role in tumorigenesis and can be targeted by rapamycin. However, the underlying mechanism of how long noncoding RNA (lncRNAs) regulate the AKT\u2010mTORC1 pathway remains unclear. <jats:italic>EPIC1<\/jats:italic> (epigenetically\u2010induced lncRNA 1) is a Myc\u2010binding lncRNA, which has been previously demonstrated to be overexpressed in multiple cancer types. In a pathway analysis including 4962 cancer patients, we observed that lncRNA <jats:italic>EPIC1<\/jats:italic> expression was positively correlated with the AKT\u2010mTORC1 signaling pathway in more than 10 cancer types, including breast and ovarian cancers. RNA\u2010seq analysis of breast and ovarian cancer cells demonstrated that <jats:italic>EPIC1\u2010<\/jats:italic>knockdown led to the downregulation of genes in the AKT\u2010mTORC1 signaling pathway. In MCF\u20107, OVCAR4, and A2780cis cell lines, <jats:italic>EPIC1<\/jats:italic> knockdown and overexpression, respectively, inhibited and activated phosphorylated AKT and the downstream phosphorylation levels of 4EBP1 and S6K. Further knockdown of Myc abolished the <jats:italic>EPIC1<\/jats:italic>\u2032s regulation of AKT\u2010mTORC1 signaling; suggested that the regulation of phosphorylation level of AKT, 4EBP1, and S6K by <jats:italic>EPIC1<\/jats:italic> depended on the expression of Myc. Moreover, <jats:italic>EPIC1<\/jats:italic> overexpressed MCF\u20107, A2780cis, and OVCAR4 cells treated with rapamycin showed a significant decreasing in rapamycin mediated inhibition of p\u2010S6K and p\u2010S6 comparing with the control group. In addition, Colony Formation assay and MTT assay indicated that <jats:italic>EPIC1<\/jats:italic> overexpression led to rapamycin resistance in breast and ovarian cancer cell lines. Our results demonstrated the lncRNA <jats:italic>EPIC1<\/jats:italic> expression activated the AKT\u2010mTORC1 signaling pathway through Myc and led to rapamycin resistance in breast and ovarian cancer.<\/jats:p>","DOI":"10.1002\/mc.23248","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T13:55:10Z","timestamp":1598622910000},"page":"1188-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["MYC\u2010binding lncRNA EPIC1 promotes AKT\u2010mTORC1 signaling and rapamycin resistance in breast and ovarian cancer"],"prefix":"10.1002","volume":"59","author":[{"given":"Yifei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center for Pharmacogenetics University of Pittsburgh  Pittsburgh 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