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Hormones and sex chromosomal differences are suggested to mediate these differences, but the functional skeletal muscle markers to document these differences are unknown. We show that the myogenic microRNA miR-486 is a marker of sex-specific differences in cancer-induced skeletal muscle defects. Cancer-induced loss of circulating miR-486 was more severe in men with bladder, lung, and pancreatic cancers compared to women with the same cancer types. In a syngeneic model of pancreatic cancer, circulating and skeletal muscle loss of miR-486 was more severe in male mice compared to female mice. Estradiol (E2) and the clinically used selective estrogen receptor modulator toremifene increased miR-486 in undifferentiated and differentiated myoblast cell line C2C12 and E2-inducible expression correlated with direct binding of estrogen receptor alpha (ER\u03b1) to the regulatory region of the miR-486 gene. E2 and toremifene reduced the actions of cytokines such as myostatin, transforming growth factor \u03b2, and tumor necrosis factor \u03b1, which mediate cancer-induced skeletal muscle wasting. E2- and toremifene-treated C2C12 myoblast\/myotube cells contained elevated levels of active protein kinase B (AKT) with a corresponding decrease in the levels of its negative regulator PTEN, which is a target of miR-486. We propose an ER\u03b1:E2-miR-486-AKT signaling axis, which reduces the deleterious effects of cancer-induced cytokines\/chemokines on skeletal muscle mass and\/or function.<\/jats:p>","DOI":"10.1210\/endocr\/bqab142","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T17:03:46Z","timestamp":1626368626000},"source":"Crossref","is-referenced-by-count":10,"title":["Hormonally Regulated Myogenic miR-486 Influences Sex-specific Differences in Cancer-induced Skeletal Muscle Defects"],"prefix":"10.1210","volume":"162","author":[{"given":"Ruizhong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine , Indianapolis, Indiana 46202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poornima","family":"Bhat-Nakshatri","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine , Indianapolis, Indiana 46202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine , Indianapolis, Indiana 46202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine , Indianapolis, Indiana 46202 , USA"},{"name":"Richard L Roudebush VA Medical Center , Indianapolis, Indiana 46202 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-0052","authenticated-orcid":false,"given":"Harikrishna","family":"Nakshatri","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine , Indianapolis, Indiana 46202 , USA"},{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis, 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