{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:48:16Z","timestamp":1794314896844,"version":"4.9.0"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T00:00:00Z","timestamp":1615680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs.<\/jats:p>","DOI":"10.3390\/ijms22062944","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T22:13:10Z","timestamp":1615759990000},"page":"2944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway"],"prefix":"10.3390","volume":"22","author":[{"given":"Yunxia","family":"Ma","sequence":"first","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8274-8271","authenticated-orcid":false,"given":"Desiree Charlotte","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7976-2611","authenticated-orcid":false,"given":"Miljana","family":"Nenkov","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8931-5396","authenticated-orcid":false,"given":"Maryam Noor","family":"Rizwan","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abubrig","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Sonnemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Children\u2019s Clinic, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-1419","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Murrieta-Coxca","sequence":"additional","affiliation":[{"name":"Placenta-Labor, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7348-059X","authenticated-orcid":false,"given":"Diana M.","family":"Morales-Prieto","sequence":"additional","affiliation":[{"name":"Placenta-Labor, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Westermann","sequence":"additional","affiliation":[{"name":"Electron Microscopy Center, Jena University Hospital, Ziegelm\u00fchlenweg 1, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Ga\u00dfler","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-9222","authenticated-orcid":false,"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.trecan.2019.06.001","article-title":"Targeting Metabolic Bottlenecks in Lung Cancer","volume":"5","author":"Sayin","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"WHO Panel. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"943","DOI":"10.2147\/CMAR.S187317","article-title":"Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades","volume":"11","author":"Lu","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1159\/000070306","article-title":"Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer","volume":"64","author":"Chen","year":"2003","journal-title":"Oncology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/ijc.22753","article-title":"Homeobox gene HOP has a potential tumor suppressive activity in human lung cancer","volume":"121","author":"Chen","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/path.4469","article-title":"HOPX is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer","volume":"235","author":"Chen","year":"2015","journal-title":"J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1006\/geno.1998.5238","article-title":"Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes encoding membrane proteins related to Pmp22","volume":"49","author":"Kozak","year":"1998","journal-title":"Genomics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0014-4800(03)00009-1","article-title":"Epithelial membrane protein-2 is expressed in discrete anatomical regions of the eye","volume":"74","author":"Wadehra","year":"2003","journal-title":"Exp. Mol. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/his.12211","article-title":"Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia in nasal polyps","volume":"63","author":"Yu","year":"2013","journal-title":"Histopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0378-1119(96)00134-5","article-title":"Epithelial membrane protein-2 and epithelial membrane protein-3: Two novel members of the peripheral myelin protein 22 gene family","volume":"175","author":"Taylor","year":"1996","journal-title":"Gene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11858","DOI":"10.1073\/pnas.0502113102","article-title":"Epithelial membrane protein-1 is a biomarker of gefitinib resistance","volume":"102","author":"Jain","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.bbamcr.2016.02.007","article-title":"Epithelial membrane protein 2 regulates sphingosylphosphorylcholine-induced keratin 8phosphorylation and reorganization: Changes of PP2A expression by interaction with alpha4 and caveolin-1 in lung cancer cells","volume":"1863","author":"Lee","year":"2016","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.yexmp.2013.07.001","article-title":"Epithelial membrane protein 3 is frequently shown as promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer","volume":"95","author":"Xue","year":"2013","journal-title":"Exp. Mol. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ccell.2014.09.005","article-title":"Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis","volume":"26","author":"Melo","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.biochi.2018.05.014","article-title":"Exosomes in lung cancer diagnosis and treatment. From the translating research into future clinical practice","volume":"151","author":"Masaoutis","year":"2018","journal-title":"Biochimie"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41467-017-02583-0","article-title":"Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer","volume":"9","author":"Fang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3816\/CLC.2009.n.006","article-title":"Exosomal microRNA: A diagnostic marker for lung cancer","volume":"10","author":"Rabinowits","year":"2009","journal-title":"Clin. Lung Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"40055","DOI":"10.1074\/jbc.M105557200","article-title":"Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion","volume":"276","author":"Seigneuret","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ahmat Amin, M., Shimizu, A., and Ogita, H. (2019). The Pivotal Roles of the Epithelial Membrane Protein Family in Cancer Invasiveness and Metastasis. Cancers, 11.","DOI":"10.3390\/cancers11111620"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1007\/s13277-013-1416-5","article-title":"EMP1 inhibits nasopharyngeal cancer cell growth and metastasis through induction apoptosis and angiogenesis","volume":"35","author":"Sun","year":"2014","journal-title":"Tumour Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/jcp.2010.082404","article-title":"The expression of EMP1 is downregulated in oral squamous cell carcinoma and possibly associated with tumour metastasis","volume":"64","author":"Zhang","year":"2011","journal-title":"J. Clin. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/carcin\/bgp220","article-title":"Epigenetics in cancer","volume":"31","author":"Sharma","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e9538","DOI":"10.1097\/MD.0000000000009538","article-title":"High EMP3 expression might independently predict poor overall survival in glioblastoma and its expression is related to DNA methylation","volume":"97","author":"Yue","year":"2018","journal-title":"Medicine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28824","DOI":"10.1074\/jbc.270.48.28824","article-title":"Epithelial membrane protein-1, peripheral myelin protein 22, and lens membrane protein 20 define a novel gene family","volume":"270","author":"Taylor","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.1038\/s41388-018-0286-0","article-title":"Epithelial membrane protein 1 promotes tumor metastasis by enhancing cell migration via copine-III and Rac1","volume":"37","author":"Shimizu","year":"2018","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fu, M., Rao, R., Sudhakar, D., Hogue, C.P., Rutta, Z., Morales, S., Gordon, L.K., Braun, J., Goodglick, L., and Wadehra, M. (2011). Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019945"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/cncr.21957","article-title":"Expression of epithelial membrane protein-2 is associated with endometrial adenocarcinoma of unfavorable outcome","volume":"107","author":"Wadehra","year":"2006","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.1002\/cncr.25259","article-title":"Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development","volume":"116","author":"Habeeb","year":"2010","journal-title":"Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1010428317718404","DOI":"10.1177\/1010428317718404","article-title":"EMP3 is induced by TWIST1\/2 and regulates epithelial-to-mesenchymal transition of gastric cancer cells","volume":"39","author":"Han","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1010428317695972","DOI":"10.1177\/1010428317695972","article-title":"EMP2 re-expression inhibits growth and enhances radiosensitivity in nasopharyngeal carcinoma","volume":"39","author":"Tang","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.7150\/jca.30342","article-title":"EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy","volume":"10","author":"Wang","year":"2019","journal-title":"J. Cancer"},{"key":"ref_33","first-page":"199","article-title":"EMP1, EMP 2, and EMP3 as novel therapeutic targets in human cancer. Biochim. Biophys. Acta. Rev","volume":"1868","author":"Wang","year":"2017","journal-title":"Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ajpath.2013.05.015","article-title":"Epithelial membrane protein 2 is a prognostic indictor for patients with urothelial carcinoma of the upper urinary tract","volume":"183","author":"Wang","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BST0380217","article-title":"Regulation of cyclin D1 gene expression","volume":"38","author":"Witzel","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1038\/sj.onc.1205907","article-title":"Post-transcriptional regulation of cyclin D1 expression during G2 phase","volume":"21","author":"Guo","year":"2002","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s12967-020-02426-5","article-title":"Tumor cells derived-exosomes as angiogenenic agents: Possible therapeutic implications","volume":"18","author":"Ahmadi","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_38","first-page":"10:1500","article-title":"Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?","volume":"20","author":"Kamal","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1159\/000494875","article-title":"Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: A Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments","volume":"50","author":"Gao","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_40","first-page":"98","article-title":"Clinically Significant Dysregulation of hsa-miR-30d-5p and hsa-let-7b Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer","volume":"10","author":"Hosseini","year":"2018","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1007\/s10529-017-2428-9","article-title":"Non-small cell lung cancer: miR-30d suppresses tumor invasion and migration by directly targeting NFIB","volume":"39","author":"Wu","year":"2017","journal-title":"Biotechnol. Lett."},{"key":"ref_42","first-page":"2211","article-title":"miR-802 inhibits the aggressive behaviors of non-small cell lung cancer cells by directly targeting FGFR1","volume":"54","author":"Zhang","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_43","first-page":"1497","article-title":"MicroRNA-200a suppresses migration and invasion and enhances the radiosensitivity of NSCLC cells by inhibiting the HGF\/c-Met signaling pathway","volume":"41","author":"Du","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fonc.2016.00003","article-title":"MicroRNA Targeting to Modulate Tumor Microenvironment","volume":"6","author":"Kuninty","year":"2016","journal-title":"Front. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e4196","DOI":"10.7717\/peerj.4196","article-title":"Exosomal microRNA remodels the tumor microenvironment","volume":"5","author":"Jiang","year":"2017","journal-title":"PeerJ"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/1878-0261.12632","article-title":"Downregulation of circulating miR 802-5p and miR 194-5p and upregulation of brain MEF2C along breast cancer brain metastasization","volume":"14","author":"Sereno","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Conti, I., Varano, G., Simioni, C., Laface, I., Milani, D., Rimondi, E., and Neri, L.M. (2020). miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment. Cells, 9.","DOI":"10.3390\/cells9010220"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"14448","DOI":"10.1038\/ncomms14448","article-title":"MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression","volume":"8","author":"Teng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_49","first-page":"2528","article-title":"Exosomes isolated from CAPS1-overexpressing colorectal cancer cells promote cell migration","volume":"42","author":"Wu","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1158\/1535-7163.MCT-13-0199","article-title":"Rationale and preclinical efficacy of a novel anti-EMP2 antibody for the treatment of invasive breast cancer","volume":"13","author":"Fu","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00292-012-1586-8","article-title":"Evaluation eines Zellblockverfahrens in der zytologischen Diagnostik [Evaluation of a cell block method in cytological diagnostics]","volume":"33","author":"Weihmann","year":"2012","journal-title":"Pathologe"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/bjc.2013.369","article-title":"Circulating microRNAs predict biochemical recurrence in prostate cancer patients","volume":"109","author":"Selth","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_53","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":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/bjc.2011.28","article-title":"DSC3 expression is regulated by p53, and methylation of DSC3 DNA is a prognostic marker in human colorectal cancer","volume":"104","author":"Cui","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_55","unstructured":"Bonifacino, J.S., Dasso, M., Lippincott-Schwartz, J., Harford, J.B., and Yamada, K.M. (2006). Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids. Current Protocols in Cell Biology, Wiley. Unit 3.22."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Chaiwangyen, W., Murrieta-Coxca, J.M., Favaro, R.R., Photini, S.M., Guti\u00e9rrez-Samudio, R.N., Schleussner, E., Markert, U.R., and Morales-Prieto, D.M. (2020). MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103458"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/2944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:28Z","timestamp":1760160928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/2944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,14]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22062944"],"URL":"https:\/\/doi.org\/10.3390\/ijms22062944","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,14]]}}}