{"data":{"id":"10.6084/m9.figshare.1601869","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1601869","prefix":"10.6084","suffix":"m9.figshare.1601869","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Lu, Yuntao","givenName":"Yuntao","familyName":"Lu","affiliation":[],"nameIdentifiers":[]},{"name":"Xiao, Limin","givenName":"Limin","familyName":"Xiao","affiliation":[],"nameIdentifiers":[]},{"name":"Liu, Yawei","givenName":"Yawei","familyName":"Liu","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Hai","givenName":"Hai","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Li, Hong","givenName":"Hong","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Zhou, Qiang","givenName":"Qiang","familyName":"Zhou","affiliation":[],"nameIdentifiers":[]},{"name":"Pan, Jun","givenName":"Jun","familyName":"Pan","affiliation":[],"nameIdentifiers":[]},{"name":"Lei, Bingxi","givenName":"Bingxi","familyName":"Lei","affiliation":[],"nameIdentifiers":[]},{"name":"Huang, Annie","givenName":"Annie","familyName":"Huang","affiliation":[],"nameIdentifiers":[]},{"name":"Qi, Songtao","givenName":"Songtao","familyName":"Qi","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"\u003ci\u003eMIR517C\u003c/i\u003e inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2016,"subjects":[{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Physiology"},{"subject":"Pharmacology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Biological Sciences not elsewhere classified"},{"subject":"Developmental Biology"},{"subject":"Cancer"}],"contributors":[],"dates":[{"date":"2016-01-29","dateType":"Created"},{"date":"2023-05-30","dateType":"Updated"},{"date":"2016","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15548627.2015.1108507","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["73029779 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of \u003ci\u003eMIR517C/miR-517c\u003c/i\u003e, which belongs to the \u003ci\u003eC19MC\u003c/i\u003e microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that \u003ci\u003eMIR517C\u003c/i\u003e was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), \u003ci\u003eMIR517C\u003c/i\u003e degraded \u003ci\u003eKPNA2\u003c/i\u003e (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) \u003ci\u003eTP53\u003c/i\u003e, but not in U251 cells harboring mutant (MU) \u003ci\u003eTP53\u003c/i\u003e. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by \u003ci\u003eMIR517C\u003c/i\u003e in U87 cells. Compared with \u003ci\u003eMIR517C\u003c/i\u003e overexpression, \u003ci\u003eMIR517C\u003c/i\u003e knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in \u003ci\u003eTP53\u003c/i\u003e\u003csup\u003e\u003ci\u003e+/+\u003c/i\u003e\u003c/sup\u003e and \u003ci\u003eTP53\u003c/i\u003e\u003csup\u003e\u003ci\u003e-/-\u003c/i\u003e\u003c/sup\u003e HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT \u003ci\u003eTP53\u003c/i\u003e GBM cells and provided evidence for the signaling pathway (\u003ci\u003eMIR517C\u003c/i\u003e-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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