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dc.contributor.authorFarina, Nicholas H.
dc.contributor.authorZingiryan, Areg
dc.contributor.authorAkech, Jacqueline
dc.contributor.authorCallahan, Cody J.
dc.contributor.authorLu, Huimin
dc.contributor.authorStein, Janet L.
dc.contributor.authorLanguino, Lucia R.
dc.contributor.authorStein, Gary S.
dc.contributor.authorLian, Jane B.
dc.date2022-08-11T08:09:46.000
dc.date.accessioned2022-08-23T16:42:50Z
dc.date.available2022-08-23T16:42:50Z
dc.date.issued2016-10-25
dc.date.submitted2017-02-10
dc.identifier.citationOncotarget. 2016 Oct 25;7(43):70462-70474. doi: 10.18632/oncotarget.11992. <a href="http://dx.doi.org/10.18632/oncotarget.11992">Link to article on publisher's site</a>
dc.identifier.issn1949-2553 (Linking)
dc.identifier.doi10.18632/oncotarget.11992
dc.identifier.pmid27634876
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40173
dc.description.abstractWhile decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27634876&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectAR
dc.subjectPTEN
dc.subjectTRAMP
dc.subjectmiRNA targeting Runx
dc.subjectprostate cancer progression
dc.subjectCancer Biology
dc.titleA microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice
dc.typeJournal Article
dc.source.journaltitleOncotarget
dc.source.volume7
dc.source.issue43
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3976&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2971
dc.identifier.contextkey9667420
refterms.dateFOA2022-08-23T16:42:51Z
html.description.abstract<p>While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.</p>
dc.identifier.submissionpathoapubs/2971
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages70462-70474


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