{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:05:23Z","timestamp":1784037923193,"version":"3.55.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"11-12","license":[{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T00:00:00Z","timestamp":1570752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81700574"],"award-info":[{"award-number":["81700574"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U140322"],"award-info":[{"award-number":["U140322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Apoptosis"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased levels of cleaved Caspase 3 and the decreased of Bcl-2. To further investigate the roles of PP2A and Akt in regulating apoptosis of hepatocytes after BD, we cultivated human liver cell line L02 with serum deprivation and hypoxia, to simulate the ischemic and hypoxic conditions of hepatocytes in DBD. Increased apoptosis and decreased viability were observed during the time in this model. Meanwhile PP2A activity and Akt activity were respectively increased and decreased. Notably, the proportion of Akt phosphorylation at Ser473 decreased, while other known targets of PP2A (p38, JNK and ERK) were not affected in terms of protein levels or phosphorylation. These results suggested that PP2A is involved in apoptotic induction of hepatocytes after brain death by specific suppression of Akt. This discovery was further confirmed with pharmaceutical and genetic methods. Our work implied potential targets for reducing liver cell apoptosis and improving organ donor quality after BD.<\/jats:p>","DOI":"10.1007\/s10495-019-01570-8","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T14:04:47Z","timestamp":1570802687000},"page":"921-933","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-1423","authenticated-orcid":false,"given":"Yan","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaruo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifa","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"issue":"suppl 1","key":"1570_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/ajt.12581","volume":"14","author":"WR Kim","year":"2014","unstructured":"Kim WR, Smith JM, Skeans MA et al (2014) OPTN\/SRTR 2012 annual data report: liver. Am J Transplant 14(suppl 1):69\u201396","journal-title":"Am J Transplant"},{"issue":"suppl 1","key":"1570_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/ajt.12579","volume":"14","author":"AJ Matas","year":"2014","unstructured":"Matas AJ, Smith JM, Skeans MA et al (2014) OPTN\/SRTR 2012 annual data report: kidney. Am J Transplant 14(suppl 1):11\u201344","journal-title":"Am J Transplant"},{"issue":"suppl 1","key":"1570_CR3","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/ajt.12583","volume":"14","author":"M Colvin-Adams","year":"2014","unstructured":"Colvin-Adams M, Smithy JM, Heubner BM et al (2014) OPTN\/SRTR 2012 annual data report: heart. Am J Transplant 14(suppl 1):113\u2013138","journal-title":"Am J Transplant"},{"key":"1570_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/lt.23777","volume":"20","author":"PL Abt","year":"2014","unstructured":"Abt PL, Praestgaard J, West S, Hasz R (2014) Donor hemodynamic profile presages graft survival in donation after cardiac death liver transplantation. Liver Transpl 20:165\u2013172","journal-title":"Liver Transpl"},{"key":"1570_CR5","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.trim.2011.03.001","volume":"24","author":"J Damman","year":"2011","unstructured":"Damman J, Hoeger S, Boneschansker L et al (2011) Targeting complement activation in brain-dead donors improves renal function after transplantation. Transpl Immunol 24:233\u2013237","journal-title":"Transpl Immunol"},{"key":"1570_CR6","doi-asserted-by":"publisher","first-page":"e28518","DOI":"10.1371\/journal.pone.0028518","volume":"6","author":"S Perk","year":"2011","unstructured":"Perk S, Izamis ML, Tolboom H et al (2011) A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers. PLoS ONE 6:e28518","journal-title":"PLoS ONE"},{"key":"1570_CR7","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3727\/096368910X508889","volume":"19","author":"Y Saito","year":"2010","unstructured":"Saito Y, Goto M, Maya K et al (2010) Brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets. Cell Transplant 19:775\u2013782","journal-title":"Cell Transplant"},{"key":"1570_CR8","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.transproceed.2013.02.028","volume":"45","author":"N Ishikawa","year":"2013","unstructured":"Ishikawa N, Yagisawa T, Kimura T et al (2013) Kidney transplantation of living unrelated and ABO-incompatible donor-recipient combinations. Transplant Proc. 45:1242\u20131244","journal-title":"Transplant Proc."},{"key":"1570_CR9","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1111\/jgs.13657","volume":"63","author":"MA McAdams-DeMarco","year":"2015","unstructured":"McAdams-DeMarco MA, Isaacs K, Darko L et al (2015) Changes in frailty after kidney transplantation. J Am Geriatr Soc 63:2152\u20132157","journal-title":"J Am Geriatr Soc"},{"key":"1570_CR10","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1097\/SHK.0b013e3181b65b99","volume":"33","author":"C Adrie","year":"2010","unstructured":"Adrie C, Monchi M, Fulgencio JP et al (2010) Immune status and apoptosis activation during brain death. Shock 33:353\u2013362","journal-title":"Shock"},{"key":"1570_CR11","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.1016\/j.transproceed.2014.04.016","volume":"46","author":"S Cao","year":"2014","unstructured":"Cao S, Wang T, Yan B, Lu Y, Zhao Y, Zhang S (2014) Brain death is associated with endoplasmic reticulum stress and apoptosis in rat liver. Transplant Proc 46:3297\u20133302","journal-title":"Transplant Proc"},{"key":"1570_CR12","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1172\/JCI6974","volume":"104","author":"MA Daemen","year":"1999","unstructured":"Daemen MA, van\u2019t Veer C, Denecker G et al (1999) Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest 104:541\u2013549","journal-title":"J Clin Invest"},{"key":"1570_CR13","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s11684-011-0109-y","volume":"5","author":"SJ Zhang","year":"2011","unstructured":"Zhang SJ, Wang T (2011) The influence of brain death on donor liver and the potential mechanisms of protective intervention. Front Med 5:8\u201314","journal-title":"Front Med"},{"key":"1570_CR14","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1111\/febs.13573","volume":"283","author":"J Sangodkar","year":"2016","unstructured":"Sangodkar J, Farrington CC, McClinch K, Galsky MD, Kastrinsky DB, Narla G (2016) All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase. FEBS J 283:1004\u20131024","journal-title":"FEBS J"},{"key":"1570_CR15","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.molcel.2009.02.015","volume":"33","author":"DM Virshup","year":"2009","unstructured":"Virshup DM, Shenolikar S (2009) From promiscuity to precision: protein phosphatases get a makeover. Mol Cell 33:537\u2013545","journal-title":"Mol Cell"},{"key":"1570_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3109\/10409238.2016.1143913","volume":"51","author":"N Wlodarchak","year":"2016","unstructured":"Wlodarchak N, Xing Y (2016) PP2A as a master regulator of the cell cycle. Crit Rev Biochem Mol Biol 51:162\u2013184","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"1570_CR17","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.cell.2009.10.006","volume":"139","author":"Y Shi","year":"2009","unstructured":"Shi Y (2009) Serine\/threonine phosphatases: mechanism through structure. Cell 139:468\u2013484","journal-title":"Cell"},{"key":"1570_CR18","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.3892\/ijo.2015.2814","volume":"46","author":"G Meng","year":"2015","unstructured":"Meng G, Wang W, Chai K, Yang S, Li F, Jiang K (2015) Combination treatment with triptolide and hydroxycamptothecin synergistically enhances apoptosis in A549 lung adenocarcinoma cells through PP2A-regulated ERK, p38 MAPKs and Akt signaling pathways. Int J Oncol 46:1007\u20131017","journal-title":"Int J Oncol"},{"key":"1570_CR19","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/fonc.2016.00078","volume":"6","author":"E Arriazu","year":"2016","unstructured":"Arriazu E, Pippa R, Odero MD (2016) Protein phosphatase 2A as a therapeutic target in acute myeloid leukemia. Front Oncol 6:78","journal-title":"Front Oncol"},{"key":"1570_CR20","doi-asserted-by":"publisher","first-page":"18859","DOI":"10.1074\/jbc.M512543200","volume":"281","author":"M Xin","year":"2006","unstructured":"Xin M, Deng X (2006) Protein phosphatase 2A enhances the proapoptotic function of Bax through dephosphorylation. J Biol Chem 281:18859\u201318867","journal-title":"J Biol Chem"},{"key":"1570_CR21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1126\/scisignal.2003085","volume":"5","author":"SJ Humphrey","year":"2012","unstructured":"Humphrey SJ, James DE (2012) Uncaging akt. Sci Signal 5:20","journal-title":"Sci Signal"},{"key":"1570_CR22","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","volume":"129","author":"BD Manning","year":"2007","unstructured":"Manning BD, Cantley LC (2007) AKT\/PKB signaling: navigating downstream. Cell 129:1261\u20131274","journal-title":"Cell"},{"key":"1570_CR23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cell.2014.11.053","volume":"160","author":"J Yang","year":"2015","unstructured":"Yang J, Wu Z, Renier N et al (2015) Pathological axonal death through a MAPK cascade that triggers a local energy deficit. Cell 160:161\u2013176","journal-title":"Cell"},{"key":"1570_CR24","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/hep.26352","volume":"58","author":"YW Wang","year":"2013","unstructured":"Wang YW, Lin KT, Chen SC et al (2013) Overexpressed-eIF3I interacted and activated oncogenic Akt1 is a theranostic target in human hepatocellular carcinoma. Hepatology 58:239\u2013250","journal-title":"Hepatology"},{"key":"1570_CR25","first-page":"68","volume":"7","author":"MD Dennis","year":"2014","unstructured":"Dennis MD, Coleman CS, Berg A, Jefferson LS, Kimball SR (2014) REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to repress mTORC1 signaling. Sci Signal 7:68","journal-title":"Sci Signal"},{"key":"1570_CR26","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.neurobiolaging.2010.01.016","volume":"33","author":"GP Liu","year":"2012","unstructured":"Liu GP, Wei W, Zhou X et al (2012) I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis. Neurobiol Aging 33:254\u2013264","journal-title":"Neurobiol Aging"},{"key":"1570_CR27","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.2337\/db11-1399","volume":"61","author":"QJ Zhang","year":"2012","unstructured":"Zhang QJ, Holland WL, Wilson L et al (2012) Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. Diabetes 61:1848\u20131859","journal-title":"Diabetes"},{"key":"1570_CR28","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3892\/ijmm.2014.1806","volume":"34","author":"B Du","year":"2014","unstructured":"Du B, Li L, Zhong Z et al (2014) Brain death induces the alteration of liver protein expression profiles in rabbits. Int J Mol Med 34:578\u2013584","journal-title":"Int J Mol Med"},{"key":"1570_CR29","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1097\/00007890-200002150-00020","volume":"69","author":"J Pratschke","year":"2000","unstructured":"Pratschke J, Wilhelm MJ, Kusaka M, Laskowski I, Tilney NL (2000) A model of gradual onset brain death for transplant-associated studies in rats. Transplantation 69:427\u2013430","journal-title":"Transplantation"},{"key":"1570_CR30","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3892\/mmr.2015.4587","volume":"13","author":"Q Tu","year":"2016","unstructured":"Tu Q, Xiong Y, Fan L et al (2016) Peroxiredoxin 6 attenuates ischemia and hypoxiainduced liver damage of braindead donors. Mol Med Rep 13:753\u2013761","journal-title":"Mol Med Rep"},{"key":"1570_CR31","doi-asserted-by":"publisher","first-page":"10581","DOI":"10.1073\/pnas.1202810109","volume":"109","author":"H Jo","year":"2012","unstructured":"Jo H, Mondal S, Tan D et al (2012) Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci USA 109:10581\u201310586","journal-title":"Proc Natl Acad Sci USA"},{"key":"1570_CR32","doi-asserted-by":"publisher","first-page":"e0162658","DOI":"10.1371\/journal.pone.0162658","volume":"11","author":"Y Guo","year":"2016","unstructured":"Guo Y, Deng Y, Li X et al (2016) Glutaminolysis Was induced by TGF-beta1 through PP2Ac regulated Raf-MEK-ERK signaling in endothelial cells. PLoS ONE 11:e0162658","journal-title":"PLoS ONE"},{"key":"1570_CR33","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1194\/jlr.M300347-JLR200","volume":"45","author":"CE Chalfant","year":"2004","unstructured":"Chalfant CE, Szulc Z, Roddy P, Bielawska A, Hannun YA (2004) The structural requirements for ceramide activation of serine-threonine protein phosphatases. J Lipid Res 45:496\u2013506","journal-title":"J Lipid Res"},{"key":"1570_CR34","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1016\/j.transproceed.2016.03.054","volume":"48","author":"X Liu","year":"2016","unstructured":"Liu X, Wang B, Zhang X et al (2016) Liver transplantation using donation after brain and cardiac death: a single-center experience in China. Transplant Proc 48:1879\u20131886","journal-title":"Transplant Proc"},{"key":"1570_CR35","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/lt.24494","volume":"22","author":"JR Scalea","year":"2016","unstructured":"Scalea JR, Redfield RR, Foley DP (2016) Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers. Liver Transplant 22:1197\u20131204","journal-title":"Liver Transplant"},{"key":"1570_CR36","doi-asserted-by":"publisher","first-page":"e0148815","DOI":"10.1371\/journal.pone.0148815","volume":"11","author":"J Xu","year":"2016","unstructured":"Xu J, Sayed BA, Casas-Ferreira AM et al (2016) The impact of ischemia\/reperfusion injury on liver allografts from deceased after cardiac death versus deceased after brain death donors. PLoS ONE 11:e0148815","journal-title":"PLoS ONE"},{"key":"1570_CR37","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1111\/j.1600-6143.2007.01799.x","volume":"7","author":"S Weiss","year":"2007","unstructured":"Weiss S, Kotsch K, Francuski M et al (2007) Brain death activates donor organs and is associated with a worse I\/R injury after liver transplantation. Am J Transplant 7:1584\u20131593","journal-title":"Am J Transplant"},{"key":"1570_CR38","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1016\/j.transproceed.2007.07.044","volume":"39","author":"A Sanchez-Fructuoso","year":"2007","unstructured":"Sanchez-Fructuoso A, Naranjo Garcia P, Calvo Romero N et al (2007) Effect of the brain-death process on acute rejection in renal transplantation. Transplant Proc 39:2214\u20132216","journal-title":"Transplant Proc"},{"key":"1570_CR39","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1097\/01.tp.0000237195.12342.f1","volume":"82","author":"D Novitzky","year":"2006","unstructured":"Novitzky D, Cooper DK, Rosendale JD, Kauffman HM (2006) Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation 82:1396\u20131401","journal-title":"Transplantation"},{"key":"1570_CR40","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1600-6143.2005.01208.x","volume":"6","author":"K Kotsch","year":"2006","unstructured":"Kotsch K, Francuski M, Pascher A et al (2006) Improved long-term graft survival after HO-1 induction in brain-dead donors. Am J Transplant 6:477\u2013486","journal-title":"Am J Transplant"},{"key":"1570_CR41","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1097\/01.TP.0000080983.14161.95","volume":"76","author":"JA Van Der Hoeven","year":"2003","unstructured":"Van Der Hoeven JA, Moshage H, Schuurs T, Nijboer M, Van Schilfgaarde R, Ploeg RJ (2003) Brain death induces apoptosis in donor liver of the rat. Transplantation 76:1150\u20131154","journal-title":"Transplantation"},{"key":"1570_CR42","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.bbacli.2016.08.002","volume":"6","author":"PP Ruvolo","year":"2016","unstructured":"Ruvolo PP (2016) The broken \u201cOff\u201d switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance. BBA Clin 6:87\u201399","journal-title":"BBA Clin"},{"key":"1570_CR43","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1158\/0008-5472.CAN-15-2119","volume":"76","author":"AL Hein","year":"2016","unstructured":"Hein AL, Seshacharyulu P, Rachagani S et al (2016) PR55alpha subunit of protein phosphatase 2A supports the tumorigenic and metastatic potential of pancreatic cancer cells by sustaining hyperactive oncogenic signaling. Cancer Res 76:2243\u20132253","journal-title":"Cancer Res"},{"issue":"8","key":"1570_CR44","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1073\/pnas.0611532104","volume":"104","author":"JH Ahn","year":"2007","unstructured":"Ahn JH, McAvoy T, Rakhilin SV, Nishi A, Greengard P, Nairn AC (2007) Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56delta subunit. Proc Natl Acad Sci USA 104(8):2979\u20132984","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"1570_CR45","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1124\/jpet.302.1.111","volume":"302","author":"MS Feschenko","year":"2002","unstructured":"Feschenko MS, Stevenson E, Nairn AC, Sweadner KJ (2002) A novel cAMP-stimulated pathway in protein phosphatase 2A activation. J Pharmacol Exp Ther 302(1):111\u2013118","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"1570_CR46","doi-asserted-by":"publisher","first-page":"10121","DOI":"10.1038\/s41598-017-09549-8","volume":"7","author":"V Simko","year":"2017","unstructured":"Simko V, Iuliano F, Sevcikova A et al (2017) Hypoxia induces cancer-associated cAMP\/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII. Sci Rep 7(1):10121","journal-title":"Sci Rep"},{"key":"1570_CR47","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1007\/s13238-016-0283-4","volume":"7","author":"J Wang","year":"2016","unstructured":"Wang J, Wang Z, Yu T et al (2016) Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization. Protein Cell 7:516\u2013526","journal-title":"Protein Cell"},{"key":"1570_CR48","first-page":"1689","volume":"32","author":"N Lei","year":"2014","unstructured":"Lei N, Peng B, Zhang JY (2014) CIP2A regulates cell proliferation via the AKT signaling pathway in human lung cancer. Oncol Rep 32:1689\u20131694","journal-title":"Oncol Rep"}],"container-title":["Apoptosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-019-01570-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10495-019-01570-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-019-01570-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T17:37:16Z","timestamp":1650476236000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10495-019-01570-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,11]]},"references-count":48,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1570"],"URL":"https:\/\/doi.org\/10.1007\/s10495-019-01570-8","relation":{},"ISSN":["1360-8185","1573-675X"],"issn-type":[{"value":"1360-8185","type":"print"},{"value":"1573-675X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,11]]},"assertion":[{"value":"11 October 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"No conflicts of interest, financial or otherwise, are declared by the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}