{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:01:29Z","timestamp":1782914489532,"version":"3.54.5"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T00:00:00Z","timestamp":1404864000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0101679","type":"journal-article","created":{"date-parts":[[2014,7,9]],"date-time":"2014-07-09T18:37:02Z","timestamp":1404931022000},"page":"e101679","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evidence that RASSF1C Stimulation of Lung Cancer Cell Proliferation Depends on IGFBP-5 and PIWIL1 Expression Levels"],"prefix":"10.1371","volume":"9","author":[{"given":"Mark E.","family":"Reeves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Firek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-Tai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef G.","family":"Amaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,7,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1038\/sj.onc.1204469","article-title":"The CpG island of the novel tumor suppressor gene RASSF1A is intensely methylated in primary small cell lung carcinoma","volume":"20","author":"R Dammann","year":"2001","journal-title":"Oncogene"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/jnci\/93.9.691","article-title":"Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression","volume":"93","author":"DG Burbee","year":"2001","journal-title":"J Natl Cancer Inst"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1038\/sj.onc.1204175","article-title":"Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast, and ovarian tumors","volume":"20","author":"A Agathanggelou","year":"2001","journal-title":"Oncogene"},{"key":"ref4","first-page":"5344","article-title":"Identification of novel gene expression targets for Ras association domain family 1(RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma","volume":"63","author":"A Agathanggelou","year":"2003","journal-title":"Cancer Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/77083","article-title":"Epigenetic inactivation of a RAS association domain family protein from the lung tumor suppressor locus 3p21.3","volume":"25","author":"R Dammann","year":"2000","journal-title":"Nat Genet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"7504","DOI":"10.1073\/pnas.131216298","article-title":"The candidate tumor suppressor gene, RASS1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis","volume":"98","author":"K Dreijerink","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1158\/0008-5472.92.65.1","article-title":"Tumor Susceptibility of RASSF1A Knockout Mice","volume":"65","author":"S Tommasi","year":"2005","journal-title":"Cancer Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1038\/sj.onc.1205814","article-title":"Frequent hypermethylation of the RASSF1A gene in prostate cancer","volume":"21","author":"L Liu","year":"2002","journal-title":"Oncogene"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"35669","DOI":"10.1074\/jbc.C000463200","article-title":"Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis","volume":"275","author":"MD Vos","year":"2000","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1038\/sj.onc.1207789","article-title":"Inactivation of RASSF1C during in vivo tumor growth identifies it as a tumor suppressor gene","volume":"23","author":"J Li","year":"2004","journal-title":"Oncogene"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1152\/ajplung.00072.2006","article-title":"Ras association domain family 1C protein stimulates human lung cancer cell proliferation","volume":"291","author":"YG Amaar","year":"2006","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/1756-0500-5-239","article-title":"RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1","volume":"5","author":"ME Reeves","year":"2012","journal-title":"BMC Res Notes"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1186\/1471-2407-10-562","article-title":"Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis","volume":"10","author":"ME Reeves","year":"2010","journal-title":"BMC Cancer"},{"key":"ref14","first-page":"4269","article-title":"Dual role of RASSF1 as a tumor suppressor and an oncogene in neuroendocrine tumors of the lung","volume":"30","author":"G Pelosi","year":"2010","journal-title":"Anticancer Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"145096","DOI":"10.1155\/2013\/145096","article-title":"The RASSF1 Gene and the Opposing Effects of the RASSF1A and RASSF1C Isoforms on Cell Proliferation and Apoptosis","volume":"2013","author":"ME Reeves","year":"2013","journal-title":"Mol Biol Int"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1158\/0008-5472.CAN-06-2530","article-title":"RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP","volume":"67","author":"E Estrabaud","year":"2007","journal-title":"Cancer Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrg3462","article-title":"Argonaute proteins: functional insights and emerging roles","volume":"7","author":"G Meister","year":"2013","journal-title":"Nat Rev Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/jcb.23363","article-title":"Piwis and piwi-interacting RNAs in the epigenetics of cancer","volume":"113","author":"S Siddiqi","year":"2012","journal-title":"J Cell Biochem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"33711","DOI":"10.1371\/journal.pone.0033711","article-title":"Hiwil Mediated Tumorigenesis Is Associated with DNA Hypermethyaltion","volume":"7","author":"S Siddiqi","year":"2012","journal-title":"PloS ONE"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1359\/JBMR.050311","article-title":"RAS association domain family protein, RASSF1C, is a binding partner and a potential regulator of osteoblast cell proliferation","volume":"20","author":"YG Amaar","year":"2005","journal-title":"J Bone Miner Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"266","DOI":"10.5732\/cjc.011.10405","article-title":"Functional roles and clinical values of insulin-like growth factor-binding protein-5 in different types of cancers","volume":"31(6)","author":"G G\u00fcll\u00fc","year":"2012","journal-title":"Chin J Cancer"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1742-7843.2009.00471.x","article-title":"Betulin elicits anti-cancer effects in tumour primary cultures and cell lines in vitro","volume":"105","author":"W Rzeski","year":"2009","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/j.1349-7006.2009.01144.x","article-title":"Both CD133<sup>+<\/sup> and CD133<sup>-<\/sup> subpopulations of A549 and H446 cells contain cancer-initiating cells","volume":"100","author":"X Meng","year":"2009","journal-title":"Cancer Sci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ejcts.2009.03.063","article-title":"The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer","volume":"36","author":"V Tirino","year":"2009","journal-title":"Eur J Cardiothorac Surg"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/aps.2009.177","article-title":"Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells","volume":"(1)","author":"LJ Yang","year":"2010","journal-title":"Acta Pharmacol Sin"},{"key":"ref27","article-title":"Betulinic Acid as a potent and complex antitumor phytochemical: A minireview","author":"D Gheorgheosu","year":"2014","journal-title":"Anticancer Agents Med Chem [Epub ahead of print]"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.7314\/APJCP.2013.14.2.1067","article-title":"Hiwi knockdown inhibits the growth of lung cancer in nude mice","volume":"14","author":"D Liang","year":"2013","journal-title":"Asian Pac J Cancer Prev"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.ijrobp.2010.03.005","article-title":"Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells","volume":"78()","author":"T Sanli","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1038\/bjc.2013.187","article-title":"Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK","volume":"108","author":"Y Storozhuk","year":"2013","journal-title":"Br J Cancer"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bbagen.2011.11.011","article-title":"Trichostatin A and sirtinol suppressed survivin expression through AMPK and p38MAPK in HT29 colon cancer cells","volume":"1820(2)","author":"YF Hsu","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1016\/j.cub.2009.10.040","article-title":"ATM regulates a RASSF1A-dependent DNA damage response","volume":"19(23)","author":"G Hamilton","year":"2009","journal-title":"Cuur Biol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0101679","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T03:26:31Z","timestamp":1689391591000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0101679"}},"subtitle":[],"editor":[{"given":"Pierlorenzo","family":"Pallante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,7,9]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2014,7,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0101679","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,9]]}}}