{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:20:02Z","timestamp":1790223602151,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T00:00:00Z","timestamp":1422921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Prostate Cancer United Kingdom","award":["Grant PA13-001"],"award-info":[{"award-number":["Grant PA13-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>New therapies are required for castrate\u2010resistant prostate cancer (CRPC), and growth\u2010arrest specific 5 (GAS5) lncRNA, which riborepresses androgen receptor action, may offer novel opportunities in this regard. This lncRNA promotes the apoptosis of prostate cancer cells and its levels decline as prostate cancer cells acquire castrate\u2010resistance, so that enhancing GAS5 expression may improve the effectiveness of chemotherapies. Since GAS5 is a member of the 5' terminal oligopyrimidine gene family, we have examined mTOR inhibition as a strategy to increase GAS5 expression. Furthermore, we have determined if GAS5 itself mediates the action of mTOR inhibitors, as demonstrated for other chemotherapeutic agents in prostate cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>The effects of mTOR inhibitors on GAS5 lncRNA levels and cell growth were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNAs and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>First generation mTORC1, combined mTORC1\/mTORC2 and dual PI3K\/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen\u2010dependent (LNCaP) and androgen\u2010sensitive (22Rv1) cell lines, but not in androgen\u2010independent (PC\u20103 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 lncRNA sensitized PC\u20103 and DU 145 cells to these agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      mTOR inhibition enhances GAS5 transcript levels in certain prostate cancer cell lines. This selectivity is likely to be related to endogenous GAS5 expression levels, since GAS5 lncRNA is itself required for mTOR inhibitor action in prostate cancer cells.\n                      <jats:italic>Prostate 75:693\u2013705, 2015<\/jats:italic>\n                      . \u00a9 2015 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.22952","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T12:50:52Z","timestamp":1422967852000},"page":"693-705","source":"Crossref","is-referenced-by-count":99,"title":["Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells"],"prefix":"10.1002","volume":"75","author":[{"given":"Kiren","family":"Yacqub\u2010Usman","sequence":"first","affiliation":[{"name":"School of Life Sciences Faculty of Natural Sciences and The Institute of Science and Technology in Medicine Keele University Keele Staffordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Pickard","sequence":"additional","affiliation":[{"name":"School of Life Sciences Faculty of Natural Sciences and The Institute of Science and Technology in Medicine Keele University Keele Staffordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwyn T.","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Life Sciences Faculty of Natural Sciences and The Institute of Science and Technology in Medicine Keele University Keele Staffordshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0045(199604)28:4<251::AID-PROS6>3.0.CO;2-G"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.108.005686"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810083391504"},{"key":"e_1_2_7_6_1","first-page":"378","article-title":"PI3K\u2010AKT\u2010mTOR signalling in prostate cancer progression and androgen deprivation therapy resistance","volume":"16","author":"Edlind MP","year":"2013","journal-title":"Asian J Androl"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2012.01.008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040720"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.265124"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2650"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.05.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-38"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.20481"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.621"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.233"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4501010"},{"key":"e_1_2_7_17_1","first-page":"787","article-title":"Genes specifically expressed at growtha rrest of mammalian cells","volume":"54","author":"Schneider C","year":"1988","journal-title":"Cell Death Differ"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq776"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.6897"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/nrc3195","article-title":"Are snoRNAs and snoRNA hostgenes new players in cancer?","volume":"12","author":"Williams GT","year":"2012","journal-title":"Nat Review"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.110.064055"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-2974-y"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.373"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000568"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00510.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0886"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1231"},{"issue":"5","key":"e_1_2_7_28_1","first-page":"1711","article-title":"Preincubation of pituitary tumor cells with the epidrugs zebularine and trichostatin a are permissive for retinoic acid\u2010augmented expression of the BMP\u20104 and D2R genes","volume":"154","author":"Yacqub\u2010Usman K","year":"2013","journal-title":"Cancer\u2010Oncogenes"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800909787580999"},{"key":"e_1_2_7_30_1","first-page":"4997","article-title":"Frequent inactivation of PTEN\/MMAC1 in primary prostate cancer","volume":"57","author":"Cairns P","year":"1997","journal-title":"Current Research"},{"key":"e_1_2_7_31_1","first-page":"4800","article-title":"Loss of chromosomal region 10q23\u201325 in prostate cancer","volume":"5","author":"Gray IC","year":"1995","journal-title":"Cancer Research"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.024646"},{"key":"e_1_2_7_33_1","first-page":"267","article-title":"Synthesis of the translational apparatus is regulated at the translational level","author":"Meyuhas O","year":"2000","journal-title":"Eur J Biochem"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0394"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6606076"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.03.030"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.2.1077"},{"key":"e_1_2_7_38_1","first-page":"8","article-title":"Down regulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6","author":"Liu Z","year":"2013","journal-title":"PLoS One"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1711-x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.10021\/mc.22120"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22952","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.22952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:56:05Z","timestamp":1696312565000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.22952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,3]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/pros.22952"],"URL":"https:\/\/doi.org\/10.1002\/pros.22952","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,3]]}}}