{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:14:33Z","timestamp":1790813673710,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/22814-5 and 2015\/04788-7"],"award-info":[{"award-number":["2015\/22814-5 and 2015\/04788-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007386","name":"Pro-Reitoria de Pesquisa, Universidade de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/501100007386","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["#313479\/2017-8, #306261\/2016-2 #303573\/2015-5"],"award-info":[{"award-number":["#313479\/2017-8, #306261\/2016-2 #303573\/2015-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K\/mTOR protein pathway, body and muscle wasting, fibers\u2019 cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.<\/jats:p>","DOI":"10.3390\/cancers13225728","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T11:32:03Z","timestamp":1637062323000},"page":"5728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Jo\u00e3o Lucas Penteado","family":"Gomes","sequence":"first","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Cardial","family":"Tobias","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9057-3878","authenticated-orcid":false,"given":"Tiago","family":"Fernandes","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Casanova","family":"Silveira","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo","family":"Negr\u00e3o","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"},{"name":"Heart Institute (InCor), Medical School, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-8726","authenticated-orcid":false,"given":"Roger","family":"Chammas","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Translacional em Oncologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4750-6506","authenticated-orcid":false,"given":"Patr\u00edcia Chakur","family":"Brum","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7101-312X","authenticated-orcid":false,"given":"Edilamar Menezes","family":"Oliveira","sequence":"additional","affiliation":[{"name":"School of Physical Education and Sport, University of Sao Paulo, Sao Paulo 05508-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/jcsm.12678","article-title":"Phenotypic features of cancer cachexia-related loss of skeletal muscle mass and function: Lessons from human and animal studies","volume":"12","author":"Martin","year":"2021","journal-title":"J. CachexSarcopenia Muscle"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1093\/eurheartj\/eht424","article-title":"Cancer cachexia: Getting to the heart of the matter","volume":"40","author":"Groarke","year":"2013","journal-title":"Eur. Hear. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.semcdb.2015.11.002","article-title":"Protein breakdown in cancer cachexia","volume":"54","author":"Sandri","year":"2016","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S0092-8674(01)00616-X","article-title":"microRNAs: Tiny Regulators with Great Potential","volume":"107","author":"Ambros","year":"2001","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2015.12.013","article-title":"Muscle-specific microRNAs in skeletal muscle development","volume":"410","author":"Horak","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/cphy.c150041","article-title":"Regulation of Skeletal Muscle by microRNAs","volume":"6","author":"Diniz","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1152\/physiolgenomics.00006.2017","article-title":"Cancer cachexia-induced muscle atrophy: Evidence for alterations in microRNAs important for muscle size","volume":"49","author":"Lee","year":"2017","journal-title":"Physiol. Genom."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/jcsm.12168","article-title":"Small RNAome profiling from human skeletal muscle: Novel miRNAs and their targets associated with cancer cachexia","volume":"8","author":"Narasimhan","year":"2017","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/jcsm.12227","article-title":"Circulating myomiRs: A new class of biomarkers to monitor skeletal muscle in physiology and medicine","volume":"9","author":"Siracusa","year":"2017","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5004","DOI":"10.1158\/0008-5472.CAN-08-0180","article-title":"miR-206 Expression Is Down-regulated in Estrogen Receptor \u03b1\u2013Positive Human Breast Cancer","volume":"68","author":"Kondo","year":"2008","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"H1629","DOI":"10.1152\/ajpheart.00941.2014","article-title":"Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure","volume":"309","author":"Souza","year":"2015","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1152\/japplphysiol.00346.2011","article-title":"Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice","volume":"112","author":"Cunha","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jcsm.12495","article-title":"Effects of aerobic and inspiratory training on skeletal muscle microRNA-1 and downstream-associated pathways in patients with heart failure","volume":"11","author":"Trevizan","year":"2020","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/2415246","article-title":"Obesity Downregulates MicroRNA-126 Inducing Capillary Rarefaction in Skeletal Muscle: Effects of Aerobic Exercise Training","volume":"2017","author":"Gomes","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H543","DOI":"10.1152\/ajpheart.00899.2014","article-title":"Aerobic exercise training promotes physiological cardiac remodeling involving a set of microRNAs","volume":"309","author":"Fernandes","year":"2015","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1007\/s13277-012-0458-4","article-title":"Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model","volume":"33","author":"Ma","year":"2012","journal-title":"Tumor Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/j.1440-1681.2007.04635.x","article-title":"Maximal lactate steady state in running mice: Effect of exercise training","volume":"34","author":"Ferreira","year":"2007","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1042\/bj1600447","article-title":"The maximum activities of hexokinase, phosphorylase, phosphofructokinase, glycerol phosphate dehydrogenases, lactate dehydrogenase, octopine dehydrogenase, phosphoenolpyruvate carboxykinase, nucleoside diphosphatekinase, glutamate-oxaloacetate transaminase and arginine kinase in relation to carbohydrate utilization in muscles from marine invertebrates","volume":"160","author":"Zammit","year":"1976","journal-title":"Biochem. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1161\/HYPERTENSIONAHA.111.185801","article-title":"Exercise Training Prevents the Microvascular Rarefaction in Hypertension Balancing Angiogenic and Apoptotic Factors","volume":"59","author":"Fernandes","year":"2012","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1073\/pnas.1000300107","article-title":"Regulation of PI3-kinase\/Akt signaling by muscle-enriched microRNA-486","volume":"107","author":"Small","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1172\/JCI73579","article-title":"MicroRNA-486\u2013de-pendent modulation of DOCK3\/PTEN\/AKT signaling pathways improves muscular dystrophy-associated symptoms","volume":"124","author":"Alexander","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1158\/0008-5472.CAN-13-2817","article-title":"Cancer Affects microRNA Expression, Release, and Function in Cardiac and Skeletal Muscle","volume":"74","author":"Chen","year":"2014","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.bbagrm.2008.03.001","article-title":"MicroRNA-206: The skeletal muscle-specific myomiR","volume":"1779","author":"McCarthy","year":"2008","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.3892\/mmr.2016.5369","article-title":"Upregulation of microRNA-206 enhances lipopolysaccharide-induced inflammation and release of amyloid-\u03b2 by targeting insulin-like growth factor 1 in microglia","volume":"14","author":"Xing","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/15384101.2019.1691787","article-title":"LncRNA MALAT1 regulates trophoblast cells migration and invasion via miR-206\/IGF-1 axis","volume":"19","author":"Wu","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/jnc.12662","article-title":"Serum miR-206 and other muscle-specific microRNAs as non-invasive biomarkers for Duchenne muscular dystrophy","volume":"129","author":"Hu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ng1725","article-title":"The Role of MicroRNA-1 and MicroRNA-133 in Skeletal Muscle Proliferation and Differentiation","volume":"38","author":"Chen","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1083\/jcb.200911036","article-title":"microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7","volume":"190","author":"Chen","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/jcsm.12601","article-title":"Satellite cell self-renewal in endurance exercise is mediated by inhibition of mitochondrial oxygen consumption","volume":"11","author":"Abreu","year":"2020","journal-title":"J. Cachex- Sarcopenia Muscle"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1001\/jama.2009.681","article-title":"Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women","volume":"301","author":"Kodama","year":"2009","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jphys.2014.09.005","article-title":"Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: A systematic review","volume":"60","author":"Kirkham","year":"2014","journal-title":"J. Physiother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.lfs.2014.11.029","article-title":"Aerobic exercise training as therapy for cardiac and cancer cachexia","volume":"125","author":"Alves","year":"2015","journal-title":"Life Sci."},{"key":"ref_35","first-page":"274","article-title":"MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review","volume":"1870","author":"Toiyama","year":"2018","journal-title":"Biochim. et Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/1476-4598-9-306","article-title":"Serum microRNAs as non-invasive biomarkers for cancer","volume":"9","author":"Brase","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10985","DOI":"10.2147\/CMAR.S269978","article-title":"The Diagnostic and Prognostic Value of Serum lncRNA NEAT1 in Colorectal Cancer","volume":"ume 12","author":"Wang","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_38","first-page":"1265","article-title":"miR-206 regulates the growth of the teleost tilapia (Oreochromis niloticus) through the modulation of IGF-1 gene expression","volume":"216","author":"Yan","year":"2013","journal-title":"J. Exp. Biol."},{"key":"ref_39","first-page":"9107","article-title":"MiR-206 inhibits non small cell lung cancer cell proliferation and inva-sion by targeting SOX9","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Wang, M., Tong, Y., Liu, X., Zhang, L., Dong, D., Shao, J., and Zhou, Y. (2019). miR-206 Promotes Cancer Progression by Targeting Full-Length Neurokinin-1 Receptor in Breast Cancer. Technol. Cancer Res. Treat., 18.","DOI":"10.1177\/1533033819875168"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.bbrc.2013.02.084","article-title":"miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2","volume":"433","author":"Zhou","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1002\/jcp.29239","article-title":"Characterization of C2C12 cells in simulated microgravity: Possible use for myoblast regeneration","volume":"235","author":"Calzia","year":"2020","journal-title":"J. Cell Physiol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:31:00Z","timestamp":1760167860000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/22\/5728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,16]]},"references-count":42,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cancers13225728"],"URL":"https:\/\/doi.org\/10.3390\/cancers13225728","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,16]]}}}