{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:00:34Z","timestamp":1789426834332,"version":"build-2803163510"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key\u00a0role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. <jats:italic>In silico<\/jats:italic> analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM.<\/jats:p>","DOI":"10.1038\/s41598-017-02694-0","type":"journal-article","created":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T09:22:37Z","timestamp":1496654557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism"],"prefix":"10.1038","volume":"7","author":[{"given":"Chiara","family":"De Santi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Melaiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bonotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Cascione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpiero","family":"Di Leva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Foddis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cristaudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Lucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Truini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tironi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Murer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Boldorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Cipollini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Gemignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gasparini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Mutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Landi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"2694_CR1","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/nrg2634","volume":"10","author":"CM Croce","year":"2009","unstructured":"Croce, C. M. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet \n                           10, 704\u2013714 (2009).","journal-title":"Nat Rev Genet"},{"key":"2694_CR2","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.3390\/cancers7030842","volume":"7","author":"EA Orellana","year":"2015","unstructured":"Orellana, E. A. & Kasinski, A. L. MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy. Cancers (Basel) \n                           7, 1388\u20131405 (2015).","journal-title":"Cancers (Basel)"},{"key":"2694_CR3","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1007\/s12020-015-0629-3","volume":"49","author":"M Boccellino","year":"2015","unstructured":"Boccellino, M. et al. Gene interference strategies as a new tool for the treatment of prostate cancer. Endocrine \n                           49, 588\u2013605 (2015).","journal-title":"Endocrine"},{"key":"2694_CR4","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1007\/s00018-014-1584-5","volume":"71","author":"A Truini","year":"2014","unstructured":"Truini, A. et al. Role of microRNAs in malignant mesothelioma. Cell Mol Life Sci \n                           71, 2865\u20132878 (2014).","journal-title":"Cell Mol Life Sci"},{"key":"2694_CR5","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1089\/ars.2013.5215","volume":"21","author":"M Tomasetti","year":"2014","unstructured":"Tomasetti, M. et al. MicroRNA-126 suppresses mesothelioma malignancy by targeting IRS1 and interfering with the mitochondrial function. Antioxid Redox Signal \n                           21, 2109\u20132125 (2014).","journal-title":"Antioxid Redox Signal"},{"key":"2694_CR6","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.1093\/annonc\/mdt412","volume":"24","author":"G Reid","year":"2013","unstructured":"Reid, G. et al. Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Ann Oncol \n                           24, 3128\u20133135 (2013).","journal-title":"Ann Oncol"},{"key":"2694_CR7","doi-asserted-by":"publisher","first-page":"5319","DOI":"10.1038\/onc.2013.476","volume":"33","author":"M Cioce","year":"2014","unstructured":"Cioce, M. et al. Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma. Oncogene \n                           33, 5319\u20135331 (2014).","journal-title":"Oncogene"},{"key":"2694_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/path.1810","volume":"207","author":"X Sun","year":"2005","unstructured":"Sun, X. et al. Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling. J Pathol \n                           207, 91\u2013101 (2005).","journal-title":"J Pathol"},{"key":"2694_CR9","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1016\/j.ajpath.2014.05.004","volume":"184","author":"XV Qadir","year":"2014","unstructured":"Qadir, X. V., Han, C., Lu, D., Zhang, J. & Wu, T. miR-185 inhibits hepatocellular carcinoma growth by targeting the DNMT1\/PTEN\/Akt pathway. Am J Pathol \n                           184, 2355\u20132364 (2014).","journal-title":"Am J Pathol"},{"key":"2694_CR10","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.lungcan.2012.02.022","volume":"77","author":"S Cedres","year":"2012","unstructured":"Cedres, S. et al. Exploratory analysis of activation of PTEN-PI3K pathway and downstream proteins in malignant pleural mesothelioma (MPM). Lung Cancer \n                           77, 192\u2013198 (2012).","journal-title":"Lung Cancer"},{"key":"2694_CR11","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1038\/bjc.2014.220","volume":"110","author":"S Zhou","year":"2014","unstructured":"Zhou, S. et al. Multipoint targeting of the PI3K\/mTOR pathway in mesothelioma. Br J Cancer \n                           110, 2479\u20132488 (2014).","journal-title":"Br J Cancer"},{"key":"2694_CR12","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1158\/1535-7163.MCT-14-0243","volume":"13","author":"H Tang","year":"2014","unstructured":"Tang, H. et al. miR-185 suppresses tumor proliferation by directly targeting E2F6 and DNMT1 and indirectly upregulating BRCA1 in triple-negative breast cancer. Mol Cancer Ther \n                           13, 3185\u20133197 (2014).","journal-title":"Mol Cancer Ther"},{"key":"2694_CR13","first-page":"11854","volume":"8","author":"S Li","year":"2015","unstructured":"Li, S. et al. MiR-185 acts as a tumor suppressor by targeting AKT1 in non-small cell lung cancer cells. Int J Clin Exp Pathol \n                           8, 11854\u201311862 (2015).","journal-title":"Int J Clin Exp Pathol"},{"key":"2694_CR14","first-page":"5053","volume":"8","author":"F Qiu","year":"2015","unstructured":"Qiu, F., Xiong, J. P., Deng, J. & Xiang, X. J. TRIM29 functions as an oncogene in gastric cancer and is regulated by miR-185. Int J Clin Exp Pathol \n                           8, 5053\u20135061 (2015).","journal-title":"Int J Clin Exp Pathol"},{"key":"2694_CR15","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1158\/1078-0432.CCR-14-1437","volume":"21","author":"Y Yang","year":"2015","unstructured":"Yang, Y. et al. miR-137 and miR-197 Induce Apoptosis and Suppress Tumorigenicity by Targeting MCL-1 in Multiple Myeloma. Clin Cancer Res \n                           21, 2399\u20132411 (2015).","journal-title":"Clin Cancer Res"},{"key":"2694_CR16","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/mt.2015.10","volume":"23","author":"Y Fujita","year":"2015","unstructured":"Fujita, Y. et al. The clinical relevance of the miR-197\/CKS1B\/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther \n                           23, 717\u201327 (2015).","journal-title":"Mol Ther"},{"key":"2694_CR17","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.1038\/onc.2013.451","volume":"33","author":"A Formosa","year":"2014","unstructured":"Formosa, A. et al. MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene \n                           33, 5173\u20135182 (2014).","journal-title":"Oncogene"},{"key":"2694_CR18","doi-asserted-by":"publisher","first-page":"24566","DOI":"10.1038\/srep24566","volume":"6","author":"Y Zhang","year":"2016","unstructured":"Zhang, Y. et al. MiR-299-5p regulates apoptosis through autophagy in neurons and ameliorates cognitive capacity in APPswe\/PS1dE9 mice. Sci Rep \n                           6, 24566 (2016).","journal-title":"Sci Rep"},{"key":"2694_CR19","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1002\/gcc.20669","volume":"48","author":"M Guled","year":"2009","unstructured":"Guled, M. et al. CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis. Genes Chromosomes Cancer \n                           48, 615\u2013623 (2009).","journal-title":"Genes Chromosomes Cancer"},{"key":"2694_CR20","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1165\/rcmb.2009-0060OC","volume":"42","author":"S Busacca","year":"2010","unstructured":"Busacca, S. et al. MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications. Am J Respir Cell Mol Biol \n                           42, 312\u2013319 (2010).","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2694_CR21","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1097\/JTO.0b013e31820db125","volume":"6","author":"V Balatti","year":"2011","unstructured":"Balatti, V. et al. MicroRNAs dysregulation in human malignant pleural mesothelioma. J Thorac Oncol \n                           6, 844\u2013851 (2011).","journal-title":"J Thorac Oncol"},{"key":"2694_CR22","doi-asserted-by":"publisher","first-page":"e18232","DOI":"10.1371\/journal.pone.0018232","volume":"6","author":"L Santarelli","year":"2011","unstructured":"Santarelli, L. et al. Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma. PLoS One \n                           6, e18232 (2011).","journal-title":"PLoS One"},{"key":"2694_CR23","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.jmoldx.2014.03.002","volume":"16","author":"M Andersen","year":"2014","unstructured":"Andersen, M. et al. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma. J Mol Diagn \n                           16, 418\u2013430 (2014).","journal-title":"J Mol Diagn"},{"key":"2694_CR24","first-page":"15677","volume":"8","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y., Huang, F., Wang, J., Peng, L. & Luo, H. MiR-15b mediates liver cancer cells proliferation through targeting BCL-2. Int J Clin Exp Pathol \n                           8, 15677\u201315683 (2015).","journal-title":"Int J Clin Exp Pathol"},{"key":"2694_CR25","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1038\/onc.2011.263","volume":"31","author":"L Sun","year":"2012","unstructured":"Sun, L. et al. MiR-200b and miR-15b regulate chemotherapy-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting BMI1. Oncogene \n                           31, 432\u2013445 (2012).","journal-title":"Oncogene"},{"key":"2694_CR26","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1089\/cbr.2014.1757","volume":"30","author":"G Sun","year":"2015","unstructured":"Sun, G. et al. Decreased Expression of miR-15b in Human Gliomas is Associated with Poor Prognosis. Cancer Biother Radiopharm \n                           30, 169\u2013173 (2015).","journal-title":"Cancer Biother Radiopharm"},{"key":"2694_CR27","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.clinbiochem.2012.02.009","volume":"45","author":"M Tomasetti","year":"2012","unstructured":"Tomasetti, M. et al. Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients. Clin Biochem \n                           45, 575\u2013581 (2012).","journal-title":"Clin Biochem"},{"key":"2694_CR28","doi-asserted-by":"publisher","first-page":"11873","DOI":"10.18632\/oncotarget.2662","volume":"5","author":"H Chen","year":"2014","unstructured":"Chen, H. et al. Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A. Oncotarget \n                           5, 11873\u201311885 (2014).","journal-title":"Oncotarget"},{"key":"2694_CR29","first-page":"6547","volume":"8","author":"CZ Wang","year":"2015","unstructured":"Wang, C. Z., Yuan, P. & Li, Y. miR-126 regulated breast cancer cell invasion by targeting ADAM9. Int J Clin Exp Pathol \n                           8, 6547\u20136553 (2015).","journal-title":"Int J Clin Exp Pathol"},{"key":"2694_CR30","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s13577-014-0105-z","volume":"28","author":"C Zhao","year":"2015","unstructured":"Zhao, C., Li, Y., Zhang, M., Yang, Y. & Chang, L. miR-126 inhibits cell proliferation and induces cell apoptosis of hepatocellular carcinoma cells partially by targeting Sox2. Hum Cell \n                           28, 91\u201399 (2015).","journal-title":"Hum Cell"},{"key":"2694_CR31","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.3892\/ijo.2014.2516","volume":"45","author":"LY Liu","year":"2014","unstructured":"Liu, L. Y. et al. Mir-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2. Int J Oncol \n                           45, 1257\u20131265 (2014).","journal-title":"Int J Oncol"},{"key":"2694_CR32","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/s12967-014-0259-1","volume":"12","author":"C Du","year":"2014","unstructured":"Du, C. et al. MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6 and PIK3R2. J Transl Med \n                           12, 259 (2014).","journal-title":"J Transl Med"},{"key":"2694_CR33","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.yexcr.2015.08.006","volume":"338","author":"J Wu","year":"2015","unstructured":"Wu, J. et al. MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells. Exp Cell Res \n                           338, 232\u2013238 (2015).","journal-title":"Exp Cell Res"},{"key":"2694_CR34","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1080\/15384047.2015.1046024","volume":"16","author":"Z Ye","year":"2015","unstructured":"Ye, Z. et al. Low miR-145 silenced by DNA methylation promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1. Cancer Biol Ther \n                           16, 1071\u20131079 (2015).","journal-title":"Cancer Biol Ther"},{"key":"2694_CR35","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.urolonc.2014.01.003","volume":"32","author":"B Kou","year":"2014","unstructured":"Kou, B. et al. miR-145 inhibits invasion of bladder cancer cells by targeting PAK1. Urol Oncol \n                           32, 846\u2013854 (2014).","journal-title":"Urol Oncol"},{"key":"2694_CR36","doi-asserted-by":"publisher","first-page":"2894","DOI":"10.1093\/bioinformatics\/btn553","volume":"24","author":"S Rogers","year":"2008","unstructured":"Rogers, S. et al. Investigating the correspondence between transcriptomic and proteomic expression profiles using coupled cluster models. Bioinformatics \n                           24, 2894\u20132900 (2008).","journal-title":"Bioinformatics"},{"key":"2694_CR37","doi-asserted-by":"publisher","first-page":"e7016","DOI":"10.1371\/journal.pone.0007016","volume":"4","author":"S Crispi","year":"2009","unstructured":"Crispi, S. et al. Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target. PLoS One \n                           4, e7016 (2009).","journal-title":"PLoS One"},{"key":"2694_CR38","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.drup.2008.08.002","volume":"11","author":"DJ McConkey","year":"2008","unstructured":"McConkey, D. J. & Zhu, K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat \n                           11, 164\u2013179 (2008).","journal-title":"Drug Resist Updat"},{"key":"2694_CR39","doi-asserted-by":"publisher","first-page":"e6554","DOI":"10.1371\/journal.pone.0006554","volume":"4","author":"OD R\u00f8e","year":"2009","unstructured":"R\u00f8e, O. D. et al. Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura: the emerging gene portrait of the mesothelioma phenotype. PLoS One \n                           4, e6554 (2009).","journal-title":"PLoS One"},{"key":"2694_CR40","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","volume":"387","author":"G Zalcman","year":"2016","unstructured":"Zalcman, G. et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet \n                           387, 1405\u20131414 (2016).","journal-title":"Lancet"},{"key":"2694_CR41","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1158\/0008-5472.CAN-09-3993","volume":"70","author":"HI Pass","year":"2010","unstructured":"Pass, H. I. et al. hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma. Cancer Res \n                           70, 1916\u20131921 (2010).","journal-title":"Cancer Res"},{"key":"2694_CR42","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.molonc.2014.11.007","volume":"9","author":"MB Kirschner","year":"2015","unstructured":"Kirschner, M. B. et al. MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma. Mol Oncol \n                           9, 715\u2013726 (2015).","journal-title":"Mol Oncol"},{"key":"2694_CR43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13046-015-0167-0","volume":"34","author":"H Zhou","year":"2015","unstructured":"Zhou, H. et al. A panel of eight-miRNA signature as a potential biomarker for predicting survival in bladder cancer. J Exp Clin Cancer Res \n                           34, 53 (2015).","journal-title":"J Exp Clin Cancer Res"},{"key":"2694_CR44","doi-asserted-by":"publisher","first-page":"e43812","DOI":"10.1371\/journal.pone.0043812","volume":"7","author":"T Chiyomaru","year":"2012","unstructured":"Chiyomaru, T. et al. Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151. PLoS One \n                           7, e43812 (2012).","journal-title":"PLoS One"},{"key":"2694_CR45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.bbi.2015.04.014","volume":"49","author":"J Ni","year":"2015","unstructured":"Ni, J. et al. MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun \n                           49, 75\u201385 (2015).","journal-title":"Brain Behav Immun"},{"key":"2694_CR46","doi-asserted-by":"publisher","first-page":"17743","DOI":"10.1038\/srep17743","volume":"5","author":"R Zhou","year":"2015","unstructured":"Zhou, R. et al. Mitochondria-related miR-151a-5p reduces cellular ATP production by targeting CYTB in asthenozoospermia. Sci Rep \n                           5, 17743 (2015).","journal-title":"Sci Rep"},{"key":"2694_CR47","doi-asserted-by":"publisher","first-page":"e72","DOI":"10.1038\/oncsis.2013.32","volume":"2","author":"AG Manente","year":"2013","unstructured":"Manente, A. G. et al. Estrogen receptor \u03b2 activation impairs mitochondrial oxidative metabolism and affects malignant mesothelioma cell growth in vitro and in vivo. Oncogenesis \n                           2, e72 (2013).","journal-title":"Oncogenesis"},{"key":"2694_CR48","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1172\/JCI65344","volume":"123","author":"Z Chen","year":"2013","unstructured":"Chen, Z. et al. Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis. J Clin Invest \n                           123, 1057\u20131067 (2013).","journal-title":"J Clin Invest"},{"key":"2694_CR49","doi-asserted-by":"publisher","first-page":"e1004612","DOI":"10.1371\/journal.pcbi.1004612","volume":"11","author":"C Zhao","year":"2015","unstructured":"Zhao, C. & Popel, A. S. Computational Model of MicroRNA Control of HIF-VEGF Pathway: Insights into the Pathophysiology of Ischemic Vascular Disease and Cancer. PLoS Comput Biol \n                           11, e1004612 (2015).","journal-title":"PLoS Comput Biol"},{"key":"2694_CR50","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1089\/ars.2014.6083","volume":"21","author":"S Greco","year":"2014","unstructured":"Greco, S. & Martelli, F. MicroRNAs in Hypoxia Response. Antioxid Redox Signal \n                           21, 1164\u20131166 (2014).","journal-title":"Antioxid Redox Signal"},{"key":"2694_CR51","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1161\/HYPERTENSIONAHA.113.02647","volume":"63","author":"P Xu","year":"2014","unstructured":"Xu, P. et al. Variations of microRNAs in human placentas and plasma from preeclamptic pregnancy. Hypertension \n                           63, 1276\u20131284 (2014).","journal-title":"Hypertension"},{"key":"2694_CR52","doi-asserted-by":"publisher","first-page":"9678","DOI":"10.1158\/0008-5472.CAN-08-0969","volume":"68","author":"I Graziani","year":"2008","unstructured":"Graziani, I. et al. Opposite effects of Notch-1 and Notch-2 on mesothelioma cell survival under hypoxia are exerted through the Akt pathway. Cancer Res \n                           68, 9678\u20139685 (2008).","journal-title":"Cancer Res"},{"key":"2694_CR53","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canlet.2013.07.020","volume":"339","author":"H Goudarzi","year":"2013","unstructured":"Goudarzi, H. et al. Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1\u03b1-MUC1 pathway. Cancer Lett \n                           339, 82\u201392 (2013).","journal-title":"Cancer Lett"},{"key":"2694_CR54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/117693510700300022","volume":"3","author":"R Simon","year":"2007","unstructured":"Simon, R. et al. Analysis of gene expression data using BRB-ArrayTools. Cancer Inform \n                           3, 11\u201317 (2007).","journal-title":"Cancer Inform"},{"key":"2694_CR55","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S0076-6879(06)11009-5","volume":"411","author":"AI Saeed","year":"2006","unstructured":"Saeed, A. I. et al. TM4 microarray software suite. Methods Enzymol \n                           411, 134\u2013193 (2006).","journal-title":"Methods Enzymol"},{"key":"2694_CR56","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res \n                           43, e47 (2015).","journal-title":"Nucleic Acids Res"},{"key":"2694_CR57","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","volume":"125","author":"Y Benjamini","year":"2001","unstructured":"Benjamini, Y., Drai, D., Elmer, G., Kafkafi, N. & Golani, I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res \n                           125, 279\u2013284 (2001).","journal-title":"Behav Brain Res"},{"key":"2694_CR58","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.18632\/oncotarget.1682","volume":"5","author":"P Gasparini","year":"2014","unstructured":"Gasparini, P. et al. microRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers. Oncotarget \n                           5, 1174\u20131184 (2014).","journal-title":"Oncotarget"},{"key":"2694_CR59","unstructured":"Burnham, K. P. & Anderson, D. R. In Model Selection and Multimodel Inference (2nd ed), Ch. 2, 70\u201374 (Springer-Verlag, 2002)."},{"key":"2694_CR60","doi-asserted-by":"publisher","first-page":"RESEARCH0034","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 Biol \n                           3, RESEARCH0034 (2002).","journal-title":"Genome Biol"},{"key":"2694_CR61","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","volume":"55","author":"SA Bustin","year":"2009","unstructured":"Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem \n                           55, 611\u2013622 (2009).","journal-title":"Clin Chem"},{"key":"2694_CR62","doi-asserted-by":"crossref","unstructured":"Paraskevopoulou, M.D. et al. DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows. Nucleic Acids Res \n                           41 (Web Server issue), W169\u2013173 (2013).","DOI":"10.1093\/nar\/gkt393"},{"key":"2694_CR63","doi-asserted-by":"crossref","unstructured":"Vlachos, I. S. et al. DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Res \n                           40, (Web Server issue), W498\u20134504 (2012).","DOI":"10.1093\/nar\/gks494"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02694-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02694-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02694-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T05:12:23Z","timestamp":1671772343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-02694-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,9]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["2694"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-02694-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,9]]},"assertion":[{"value":"25 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3140"}}