{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T12:07:12Z","timestamp":1773490032104,"version":"3.50.1"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T00:00:00Z","timestamp":1541462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T00:00:00Z","timestamp":1541462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK072482"],"award-info":[{"award-number":["P30 DK072482"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["ROWE15R0"],"award-info":[{"award-number":["ROWE15R0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2015\/17\/B\/NZ3\/01485"],"award-info":[{"award-number":["UMO-2015\/17\/B\/NZ3\/01485"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Small noncoding microRNAs (miRNAs) post-transcriptionally regulate a large portion of the human transcriptome. miRNAs have been shown to play an important role in the unfolded protein response (UPR), a cellular adaptive mechanism that is important in alleviating endoplasmic reticulum (ER) stress and promoting cell recovery. Another class of small noncoding RNAs, the Piwi-interacting RNAs (piRNAs) together with PIWI proteins, was originally shown to play a role as repressors of germline transposable elements. More recent studies, however, indicate that P-element induced WImpy proteins (PIWI proteins) and piRNAs also regulate mRNA levels in somatic tissues. Using genome-wide small RNA next generation sequencing, cell viability assays, and caspase activity assays in human airway epithelial cells, we demonstrate that ER stress specifically up-regulates total piRNA expression profiles, and these changes correlate with UPR-induced apoptosis as shown by up-regulation of two pro-apoptotic factor mRNAs, <jats:italic>CHOP<\/jats:italic> and <jats:italic>NOXA<\/jats:italic>. Furthermore, siRNA knockdown of <jats:italic>PIWIL2<\/jats:italic> and <jats:italic>PIWIL4<\/jats:italic>, two proteins involved in piRNA function, attenuates UPR-related cell death, inhibits piRNA expression, and inhibits the up-regulation of <jats:italic>CHOP<\/jats:italic> and <jats:italic>NOXA<\/jats:italic> mRNA expression. Hence, we provide evidence that PIWIL2 and PIWIL4 proteins, and potentially the up-regulated piRNAs, constitute a novel epigenetic mechanism that control cellular fate during the UPR.<\/jats:p>","DOI":"10.1038\/s41598-018-34861-2","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T16:04:03Z","timestamp":1541001843000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["PIWI proteins contribute to apoptosis during the UPR in human airway epithelial cells"],"prefix":"10.1038","volume":"8","author":[{"given":"Magdalena","family":"Gebert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Bartoszewska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Janaszak-Jasiecka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrianna","family":"Moszy\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Cabaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaros\u0142aw","family":"Kr\u00f3liczewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Madanecki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata J.","family":"Ochocka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-169X","authenticated-orcid":false,"given":"David K.","family":"Crossman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Collawn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2864-6757","authenticated-orcid":false,"given":"Rafal","family":"Bartoszewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,11,6]]},"reference":[{"key":"34861_CR1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.mrfmmm.2004.06.056","volume":"569","author":"M Schroder","year":"2005","unstructured":"Schroder, M. & Kaufman, R. J. ER stress and the unfolded protein response. Mutation research 569, 29\u201363, https:\/\/doi.org\/10.1016\/j.mrfmmm.2004.06.056 (2005).","journal-title":"Mutation research"},{"key":"34861_CR2","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrm2199","volume":"8","author":"D Ron","year":"2007","unstructured":"Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8, 519\u2013529, https:\/\/doi.org\/10.1038\/nrm2199 (2007).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"34861_CR3","doi-asserted-by":"publisher","unstructured":"Fonseca, S. G., Gromada, J. & Urano, F. Endoplasmic reticulum stress and pancreatic beta-cell death. Trends Endocrinol Metab, https:\/\/doi.org\/10.1016\/j.tem.2011.02.008 (2011).","DOI":"10.1016\/j.tem.2011.02.008"},{"key":"34861_CR4","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1089\/ars.2007.1782","volume":"9","author":"JD Malhotra","year":"2007","unstructured":"Malhotra, J. D. & Kaufman, R. J. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9, 2277\u20132293, https:\/\/doi.org\/10.1089\/ars.2007.1782 (2007).","journal-title":"Antioxid Redox Signal"},{"key":"34861_CR5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.tcb.2003.11.001","volume":"14","author":"DT Rutkowski","year":"2004","unstructured":"Rutkowski, D. T. & Kaufman, R. J. A trip to the ER: coping with stress. Trends in cell biology 14, 20\u201328 (2004).","journal-title":"Trends in cell biology"},{"key":"34861_CR6","doi-asserted-by":"publisher","first-page":"S102","DOI":"10.1212\/01.wnl.0000192306.98198.ec","volume":"66","author":"K Zhang","year":"2006","unstructured":"Zhang, K. & Kaufman, R. J. The unfolded protein response: a stress signaling pathway critical for health and disease. Neurology 66, S102\u2013109, https:\/\/doi.org\/10.1212\/01.wnl.0000192306.98198.ec (2006).","journal-title":"Neurology"},{"key":"34861_CR7","doi-asserted-by":"publisher","first-page":"555","DOI":"10.2478\/s11658-013-0106-z","volume":"18","author":"S Bartoszewska","year":"2013","unstructured":"Bartoszewska, S. et al. Regulation of the unfolded protein response by microRNAs. Cellular & molecular biology letters 18, 555\u2013578, https:\/\/doi.org\/10.2478\/s11658-013-0106-z (2013).","journal-title":"Cellular & molecular biology letters"},{"key":"34861_CR8","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.tibs.2015.12.008","volume":"41","author":"B Czech","year":"2016","unstructured":"Czech, B. & Hannon, G. J. One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing. Trends in biochemical sciences 41, 324\u2013337, https:\/\/doi.org\/10.1016\/j.tibs.2015.12.008 (2016).","journal-title":"Trends in biochemical sciences"},{"key":"34861_CR9","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.ejcb.2017.09.004","volume":"96","author":"M Ponnusamy","year":"2017","unstructured":"Ponnusamy, M., Yan, K. W., Liu, C. Y., Li, P. F. & Wang, K. PIWI family emerging as a decisive factor of cell fate: An overview. Eur J Cell Biol 96, 746\u2013757, https:\/\/doi.org\/10.1016\/j.ejcb.2017.09.004 (2017).","journal-title":"Eur J Cell Biol"},{"key":"34861_CR10","doi-asserted-by":"publisher","unstructured":"Burroughs, A. M., Iyer, L. M. & Aravind, L. Two novel PIWI families: roles in inter-genomic conflicts in bacteria and Mediator-dependent modulation of transcription in eukaryotes. Biol Direct 8, https:\/\/doi.org\/10.1186\/1745-6150-8-13 (2013).","DOI":"10.1186\/1745-6150-8-13"},{"key":"34861_CR11","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/nature09465","volume":"467","author":"C Rouget","year":"2010","unstructured":"Rouget, C. et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 467, 1128\u20131132, https:\/\/doi.org\/10.1038\/nature09465 (2010).","journal-title":"Nature"},{"key":"34861_CR12","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.celrep.2015.07.030","volume":"12","author":"B Barckmann","year":"2015","unstructured":"Barckmann, B. et al. Aubergine iCLIP Reveals piRNA-Dependent Decay of mRNAs Involved in Germ Cell Development in the Early Embryo. Cell reports 12, 1205\u20131216, https:\/\/doi.org\/10.1016\/j.celrep.2015.07.030 (2015).","journal-title":"Cell reports"},{"issue":"17","key":"34861_CR13","doi-asserted-by":"publisher","first-page":"dev161786","DOI":"10.1242\/dev.161786","volume":"145","author":"Patricia Rojas-R\u00edos","year":"2018","unstructured":"Rojas-Rios, P. & Simonelig, M. piRNAs and PIWI proteins: regulators of gene expression in development and stem cells. Development 145, https:\/\/doi.org\/10.1242\/dev.161786 (2018).","journal-title":"Development"},{"key":"34861_CR14","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.bbrc.2014.02.112","volume":"446","author":"C Kwon","year":"2014","unstructured":"Kwon, C. et al. Detection of PIWI and piRNAs in the mitochondria of mammalian cancer cells. Biochemical and biophysical research communications 446, 218\u2013223, https:\/\/doi.org\/10.1016\/j.bbrc.2014.02.112 (2014).","journal-title":"Biochemical and biophysical research communications"},{"key":"34861_CR15","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3389\/fgene.2012.00204","volume":"3","author":"R Suzuki","year":"2012","unstructured":"Suzuki, R., Honda, S. & Kirino, Y. PIWI Expression and Function in Cancer. Frontiers in genetics 3, 204, https:\/\/doi.org\/10.3389\/fgene.2012.00204 (2012).","journal-title":"Frontiers in genetics"},{"key":"34861_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/srep10423","volume":"5","author":"VD Martinez","year":"2015","unstructured":"Martinez, V. D. et al. Unique somatic and malignant expression patterns implicate PIWI-interacting RNAs in cancer-type specific biology. Scientific reports 5, 10423, https:\/\/doi.org\/10.1038\/srep10423 (2015).","journal-title":"Scientific reports"},{"key":"34861_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8316","volume":"6","author":"Y Mei","year":"2015","unstructured":"Mei, Y. et al. A piRNA-like small RNA interacts with and modulates p-ERM proteins in human somatic cells. Nature communications 6, 7316, https:\/\/doi.org\/10.1038\/ncomms8316 (2015).","journal-title":"Nature communications"},{"key":"34861_CR18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.canlet.2013.04.008","volume":"336","author":"Y Mei","year":"2013","unstructured":"Mei, Y., Clark, D. & Mao, L. Novel dimensions of piRNAs in cancer. Cancer letters 336, 46\u201352, https:\/\/doi.org\/10.1016\/j.canlet.2013.04.008 (2013).","journal-title":"Cancer letters"},{"key":"34861_CR19","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1113\/jphysiol.2005.096669","volume":"569","author":"Z Bebok","year":"2005","unstructured":"Bebok, Z. et al. Failure of cAMP agonists to activate rescued deltaF508 CFTR in CFBE41o- airway epithelial monolayers. The Journal of physiology 569, 601\u2013615, https:\/\/doi.org\/10.1113\/jphysiol.2005.096669 (2005).","journal-title":"The Journal of physiology"},{"key":"34861_CR20","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1165\/ajrcmb.10.1.7507342","volume":"10","author":"AL Cozens","year":"1994","unstructured":"Cozens, A. L. et al. CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells. American journal of respiratory cell and molecular biology 10, 38\u201347, https:\/\/doi.org\/10.1165\/ajrcmb.10.1.7507342 (1994).","journal-title":"American journal of respiratory cell and molecular biology"},{"key":"34861_CR21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/B978-0-12-385928-0.00001-8","volume":"491","author":"R Bartoszewski","year":"2011","unstructured":"Bartoszewski, R. et al. CFTR expression regulation by the unfolded protein response. Methods in enzymology 491, 3\u201324, https:\/\/doi.org\/10.1016\/B978-0-12-385928-0.00001-8 (2011).","journal-title":"Methods in enzymology"},{"key":"34861_CR22","doi-asserted-by":"publisher","first-page":"41862","DOI":"10.1074\/jbc.M111.304956","volume":"286","author":"R Bartoszewski","year":"2011","unstructured":"Bartoszewski, R. et al. The unfolded protein response (UPR)-activated transcription factor X-box-binding protein 1 (XBP1) induces microRNA-346 expression that targets the human antigen peptide transporter 1 (TAP1) mRNA and governs immune regulatory genes. The Journal of biological chemistry 286, 41862\u201341870, https:\/\/doi.org\/10.1074\/jbc.M111.304956 (2011).","journal-title":"The Journal of biological chemistry"},{"key":"34861_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome biology 3, RESEARCH0034 (2002).","journal-title":"Genome biology"},{"key":"34861_CR24","doi-asserted-by":"publisher","first-page":"e92128","DOI":"10.1371\/journal.pone.0092128","volume":"9","author":"R Bartoszewski","year":"2014","unstructured":"Bartoszewski, R. et al. Mangiferin has an additive effect on the apoptotic properties of hesperidin in Cyclopia sp. tea extracts. PloS one 9, e92128, https:\/\/doi.org\/10.1371\/journal.pone.0092128 (2014).","journal-title":"PloS one"},{"key":"34861_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-6-62","volume":"6","author":"A Larionov","year":"2005","unstructured":"Larionov, A., Krause, A. & Miller, W. A standard curve based method for relative real time PCR data processing. BMC bioinformatics 6, 62, https:\/\/doi.org\/10.1186\/1471-2105-6-62 (2005).","journal-title":"BMC bioinformatics"},{"key":"34861_CR26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.biocel.2009.09.013","volume":"42","author":"M Lamkanfi","year":"2010","unstructured":"Lamkanfi, M. & Kanneganti, T. D. Caspase-7: a protease involved in apoptosis and inflammation. The international journal of biochemistry & cell biology 42, 21\u201324, https:\/\/doi.org\/10.1016\/j.biocel.2009.09.013 (2010).","journal-title":"The international journal of biochemistry & cell biology"},{"key":"34861_CR27","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1093\/jb\/mvh122","volume":"136","author":"K Yamamoto","year":"2004","unstructured":"Yamamoto, K., Yoshida, H., Kokame, K., Kaufman, R. J. & Mori, K. Differential contributions of ATF6 and XBP1 to the activation of endoplasmic reticulum stress-responsive cis-acting elements ERSE, UPRE and ERSE-II. Journal of biochemistry 136, 343\u2013350, https:\/\/doi.org\/10.1093\/jb\/mvh122 (2004).","journal-title":"Journal of biochemistry"},{"key":"34861_CR28","doi-asserted-by":"publisher","first-page":"bat069","DOI":"10.1093\/database\/bat069","volume":"2013","author":"I Krystkowiak","year":"2013","unstructured":"Krystkowiak, I. et al. Nencki Genomics Database\u2013Ensembl funcgen enhanced with intersections, user data and genome-wide TFBS motifs. Database: the journal of biological databases and curation 2013, bat069, https:\/\/doi.org\/10.1093\/database\/bat069 (2013).","journal-title":"Database: the journal of biological databases and curation"},{"key":"34861_CR29","doi-asserted-by":"publisher","first-page":"W557","DOI":"10.1093\/nar\/gkt328","volume":"41","author":"K Wolstencroft","year":"2013","unstructured":"Wolstencroft, K. et al. The Taverna workflow suite: designing and executing workflows of Web Services on the desktop, web or in the cloud. Nucleic acids research 41, W557\u2013561, https:\/\/doi.org\/10.1093\/nar\/gkt328 (2013).","journal-title":"Nucleic acids research"},{"key":"34861_CR30","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","volume":"47","author":"WH Kruskal","year":"1952","unstructured":"Kruskal, W. H. & Wallis, W. A. Use of Ranks in One-Criterion Variance Analysis. J Am Stat Assoc 47, 583\u2013621 (1952).","journal-title":"J Am Stat Assoc"},{"key":"34861_CR31","doi-asserted-by":"publisher","first-page":"241","DOI":"10.2307\/1266041","volume":"6","author":"OJ Dunn","year":"1964","unstructured":"Dunn, O. J. Multiple Comparisons Using Rank Sums. Technometrics 6, 241\u2013&, https:\/\/doi.org\/10.2307\/1266041 (1964).","journal-title":"Technometrics"},{"key":"34861_CR32","doi-asserted-by":"publisher","first-page":"72","DOI":"10.2307\/1412159","volume":"15","author":"C Spearman","year":"1904","unstructured":"Spearman, C. The Proof and Measurement of Association between Two Things. The American Journal of Psychology 15, 72\u2013101, https:\/\/doi.org\/10.2307\/1412159 (1904).","journal-title":"The American Journal of Psychology"},{"key":"34861_CR33","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0378-5173(03)00129-7","volume":"257","author":"B Forbes","year":"2003","unstructured":"Forbes, B., Shah, A., Martin, G. P. & Lansley, A. B. The human bronchial epithelial cell line 16HBE14o- as a model system of the airways for studying drug transport. International journal of pharmaceutics 257, 161\u2013167 (2003).","journal-title":"International journal of pharmaceutics"},{"key":"34861_CR34","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1083\/jcb.201010055","volume":"192","author":"S Behrman","year":"2011","unstructured":"Behrman, S., Acosta-Alvear, D. & Walter, P. A CHOP-regulated microRNA controls rhodopsin expression. The Journal of Cell Biology 192, 919\u2013927, https:\/\/doi.org\/10.1083\/jcb.201010055 (2011).","journal-title":"The Journal of Cell Biology"},{"key":"34861_CR35","doi-asserted-by":"publisher","first-page":"12154","DOI":"10.1074\/jbc.M707610200","volume":"283","author":"R Bartoszewski","year":"2008","unstructured":"Bartoszewski, R. et al. The mechanism of cystic fibrosis transmembrane conductance regulator transcriptional repression during the unfolded protein response. The Journal of biological chemistry 283, 12154\u201312165, https:\/\/doi.org\/10.1074\/jbc.M707610200 (2008).","journal-title":"The Journal of biological chemistry"},{"key":"34861_CR36","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1089\/ARS.2009.2485","volume":"11","author":"M Wang","year":"2009","unstructured":"Wang, M., Wey, S., Zhang, Y., Ye, R. & Lee, A. S. Role of the unfolded protein response regulator GRP78\/BiP in development, cancer, and neurological disorders. Antioxid Redox Signal 11, 2307\u20132316, https:\/\/doi.org\/10.1089\/ARS.2009.2485 (2009).","journal-title":"Antioxid Redox Signal"},{"key":"34861_CR37","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ymeth.2004.10.010","volume":"35","author":"AS Lee","year":"2005","unstructured":"Lee, A. S. The ER chaperone and signaling regulator GRP78\/BiP as a monitor of endoplasmic reticulum stress. Methods 35, 373\u2013381, https:\/\/doi.org\/10.1016\/j.ymeth.2004.10.010 (2005).","journal-title":"Methods"},{"key":"34861_CR38","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/nrd2755","volume":"7","author":"I Kim","year":"2008","unstructured":"Kim, I., Xu, W. & Reed, J. C. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nature reviews. Drug discovery 7, 1013\u20131030, https:\/\/doi.org\/10.1038\/nrd2755 (2008).","journal-title":"Nature reviews. Drug discovery"},{"key":"34861_CR39","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","volume":"11","author":"S Oyadomari","year":"2004","unstructured":"Oyadomari, S. & Mori, M. Roles of CHOP\/GADD153 in endoplasmic reticulum stress. Cell death and differentiation 11, 381\u2013389, https:\/\/doi.org\/10.1038\/sj.cdd.4401373 (2004).","journal-title":"Cell death and differentiation"},{"key":"34861_CR40","doi-asserted-by":"publisher","first-page":"7260","DOI":"10.1074\/jbc.M509868200","volume":"281","author":"J Li","year":"2006","unstructured":"Li, J., Lee, B. & Lee, A. S. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. The Journal of biological chemistry 281, 7260\u20137270, https:\/\/doi.org\/10.1074\/jbc.M509868200 (2006).","journal-title":"The Journal of biological chemistry"},{"key":"34861_CR41","doi-asserted-by":"publisher","first-page":"3460","DOI":"10.1016\/j.bbamcr.2013.06.028","volume":"1833","author":"R Sano","year":"2013","unstructured":"Sano, R. & Reed, J. C. ER stress-induced cell death mechanisms. Biochimica et biophysica acta 1833, 3460\u20133470, https:\/\/doi.org\/10.1016\/j.bbamcr.2013.06.028 (2013).","journal-title":"Biochimica et biophysica acta"},{"key":"34861_CR42","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","volume":"11","author":"S Oyadomari","year":"2003","unstructured":"Oyadomari, S. & Mori, M. Roles of CHOP\/GADD153 in endoplasmic reticulum stress. Cell death and differentiation 11, 381, https:\/\/doi.org\/10.1038\/sj.cdd.4401373 (2003).","journal-title":"Cell death and differentiation"},{"key":"34861_CR43","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1126\/science.287.5453.664","volume":"287","author":"F Urano","year":"2000","unstructured":"Urano, F. et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287, 664\u2013666, https:\/\/doi.org\/10.1126\/science.287.5453.664 (2000).","journal-title":"Science"},{"key":"34861_CR44","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1083\/jcb.200310015","volume":"165","author":"J Hitomi","year":"2004","unstructured":"Hitomi, J. et al. Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and A\u03b2-induced cell death. The Journal of Cell Biology 165, 347\u2013356, https:\/\/doi.org\/10.1083\/jcb.200310015 (2004).","journal-title":"The Journal of Cell Biology"},{"key":"34861_CR45","doi-asserted-by":"publisher","first-page":"e73870","DOI":"10.1371\/journal.pone.0073870","volume":"8","author":"K Cawley","year":"2013","unstructured":"Cawley, K. et al. Disruption of microRNA biogenesis confers resistance to ER stress-induced cell death upstream of the mitochondrion. PloS one 8, e73870, https:\/\/doi.org\/10.1371\/journal.pone.0073870 (2013).","journal-title":"PloS one"},{"key":"34861_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/srep46080","volume":"7","author":"MV Mesitov","year":"2017","unstructured":"Mesitov, M. V. et al. Differential processing of small RNAs during endoplasmic reticulum stress. Scientific reports 7, 46080, https:\/\/doi.org\/10.1038\/srep46080 (2017).","journal-title":"Scientific reports"},{"key":"34861_CR47","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s40139-014-0046-y","volume":"2","author":"H Malhi","year":"2014","unstructured":"Malhi, H. Micrornas in Er Stress: Divergent Roles in Cell Fate Decisions. Current pathobiology reports 2, 117\u2013122 (2014).","journal-title":"Current pathobiology reports"},{"key":"34861_CR48","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/iub.1151","volume":"65","author":"AE Byrd","year":"2013","unstructured":"Byrd, A. E. & Brewer, J. W. Micro(RNA)managing Endoplasmic Reticulum Stress. IUBMB life 65, 373\u2013381, https:\/\/doi.org\/10.1002\/iub.1151 (2013).","journal-title":"IUBMB life"},{"key":"34861_CR49","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1128\/Mcb.00745-14","volume":"34","author":"SY Jiang","year":"2014","unstructured":"Jiang, S. Y. et al. Piwil2 Inhibits Keratin 8 Degradation through Promoting p38-Induced Phosphorylation To Resist Fas-Mediated Apoptosis. Mol Cell Biol 34, 3928\u20133938, https:\/\/doi.org\/10.1128\/Mcb.00745-14 (2014).","journal-title":"Mol Cell Biol"},{"key":"34861_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3945-6","volume":"18","author":"IV Gainetdinov","year":"2018","unstructured":"Gainetdinov, I. V. et al. Assessment of piRNA biogenesis and function in testicular germ cell tumors and their precursor germ cell neoplasia in situ. BMC Cancer 18, 20, https:\/\/doi.org\/10.1186\/s12885-017-3945-6 (2018).","journal-title":"BMC Cancer"},{"key":"34861_CR51","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1084\/jem.20161371","volume":"214","author":"C Carrieri","year":"2017","unstructured":"Carrieri, C. et al. A transit-amplifying population underpins the efficient regenerative capacity of the testis. The Journal of Experimental Medicine 214, 1631\u20131641, https:\/\/doi.org\/10.1084\/jem.20161371 (2017).","journal-title":"The Journal of Experimental Medicine"},{"key":"34861_CR52","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.molcel.2012.07.021","volume":"47","author":"D Olivieri","year":"2012","unstructured":"Olivieri, D., Senti, K. A., Subramanian, S., Sachidanandam, R. & Brennecke, J. The Cochaperone Shutdown Defines a Group of Biogenesis Factors Essential for All piRNA Populations in Drosophila. Mol Cell 47, 954\u2013969, https:\/\/doi.org\/10.1016\/j.molcel.2012.07.021 (2012).","journal-title":"Mol Cell"},{"key":"34861_CR53","doi-asserted-by":"publisher","first-page":"8506","DOI":"10.1128\/Mcb.22.24.8506-8513.2002","volume":"22","author":"MG Marcu","year":"2002","unstructured":"Marcu, M. G. et al. Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1 alpha. Mol Cell Biol 22, 8506\u20138513, https:\/\/doi.org\/10.1128\/Mcb.22.24.8506-8513.2002 (2002).","journal-title":"Mol Cell Biol"},{"key":"34861_CR54","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.molcel.2012.08.025","volume":"48","author":"NS Chitnis","year":"2012","unstructured":"Chitnis, N. S. et al. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell 48, 353\u2013364, https:\/\/doi.org\/10.1016\/j.molcel.2012.08.025 (2012).","journal-title":"Mol Cell"},{"key":"34861_CR55","doi-asserted-by":"publisher","first-page":"e36490","DOI":"10.1371\/journal.pone.0036490","volume":"7","author":"M Lerner","year":"2012","unstructured":"Lerner, M., Haneklaus, M., Harada, M. & Grand\u00e9r, D. MiR-200c Regulates Noxa Expression and Sensitivity to Proteasomal Inhibitors. PloS one 7, e36490, https:\/\/doi.org\/10.1371\/journal.pone.0036490 (2012).","journal-title":"PloS one"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34861-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34861-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34861-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T11:26:23Z","timestamp":1671621983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34861-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,6]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["34861"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-34861-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,6]]},"assertion":[{"value":"27 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16431"}}