{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:06:25Z","timestamp":1760058385322,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States Veterans Administration Department Merit Review Award","award":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"],"award-info":[{"award-number":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"]}]},{"DOI":"10.13039\/100015502","name":"Dialysis Clinic Inc.","doi-asserted-by":"publisher","award":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"],"award-info":[{"award-number":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"]}],"id":[{"id":"10.13039\/100015502","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"],"award-info":[{"award-number":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of New Mexico (UNM) Comprehensive Cancer Center Support","award":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"],"award-info":[{"award-number":["2I01BX001000-10","C-4149","NHLBIT32HL007736","NCI P30CA118100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 or TSC2 genes and affects multiple organs. TSC proteins control cell growth by regulating the activity of the mechanistic target of rapamycin complex 1. Extracellular vesicles (EVs) are membrane-bound particles produced by cells that mediate cellular communication, function, and growth. Although extensive studies regarding the genetic basis of TSC exist, the exact mechanism contributing to its pathogenesis remains unresolved. It has been proposed that EVs generated by renal cyst epithelia of mice and cells with Tsc gene mutations contain factors that alter the function and proliferation of TSC-sufficient cells. To test this, EVs from the kidneys and kidney explants of wildtype and Tsc1KO mice were isolated and characterized by Western blotting, transmission electron microscopy, dynamic light scattering, and fluorescent nanoparticle tracking. Our results show an enrichment in EV-associated markers and particle sizes of similar ranges. RNA-seq and proteomic analyses identified EV shuttle factors. EV RNA and protein shuttle factors showed significant differences. Furthermore, EVs isolated from Tsc1KO mice inhibited the proliferation of M-1 cells. Understanding the role of EVs in cell proliferation and cystogenesis in TSC may lead to the development of new approaches for the treatment of this disease.<\/jats:p>","DOI":"10.3390\/ijms26073154","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Extracellular Vesicles in TSC Renal Cystogenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-5107","authenticated-orcid":false,"given":"Kamyar","family":"Zahedi","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Research Services, Raymond J. Murphy Veterans Health Care Center, Albuquerque, NM 87108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie","family":"Morgan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Prieto","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6582-2281","authenticated-orcid":false,"given":"Marybeth","family":"Brooks","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Research Services, Raymond J. Murphy Veterans Health Care Center, Albuquerque, NM 87108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2138-016X","authenticated-orcid":false,"given":"Tamara A.","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5710-292X","authenticated-orcid":false,"given":"Sharon","family":"Barone","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Research Services, Raymond J. Murphy Veterans Health Care Center, Albuquerque, NM 87108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Bissler","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Sciences Center, Le Bonheur Children\u2019s Hospital, Memphis, TN 38163, USA"},{"name":"The Department of Pediatrics, St. Jude Children\u2019s Hospital, Memphis, TN 38105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9679-7805","authenticated-orcid":false,"given":"Christos","family":"Argyropoulos","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-4469","authenticated-orcid":false,"given":"Manoocher","family":"Soleimani","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"},{"name":"Research Services, Raymond J. Murphy Veterans Health Care Center, Albuquerque, NM 87108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The tuberous sclerosis complex","volume":"355","author":"Crino","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/316951","article-title":"Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs","volume":"68","author":"Dabora","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16035","DOI":"10.1038\/nrdp.2016.35","article-title":"Tuberous sclerosis complex","volume":"2","author":"Henske","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1093\/hmg\/3.suppl_1.1477","article-title":"The molecular genetics of tuberous sclerosis","volume":"3","author":"Sampson","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/sj.ki.5001853","article-title":"Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors","volume":"70","author":"Rakowski","year":"2006","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/ncb2763","article-title":"Signal integration by mTORC1 coordinates nutrient input with biosynthetic output","volume":"15","author":"Dibble","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 complex: A molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/s41581-018-0059-6","article-title":"Renal disease in tuberous sclerosis complex: Pathogenesis and therapy","volume":"14","author":"Lam","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1159\/000320891","article-title":"Tuberous sclerosis complex renal disease","volume":"118","author":"Dixon","year":"2011","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F279","DOI":"10.1152\/ajprenal.00525.2013","article-title":"Tuberous sclerosis complex, mTOR, and the kidney: Report of an NIDDK-sponsored workshop","volume":"306","author":"Henske","year":"2014","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/ajmg.c.31654","article-title":"Renal manifestation of tuberous sclerosis complex","volume":"178","author":"Bissler","year":"2018","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa063564","article-title":"Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis","volume":"358","author":"Bissler","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2020190118","DOI":"10.1073\/pnas.2020190118","article-title":"Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex","volume":"118","author":"Barone","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13983","DOI":"10.14814\/phy2.13983","article-title":"Tuberous sclerosis complex exhibits a new renal cystogenic mechanism","volume":"7","author":"Bissler","year":"2019","journal-title":"Physiol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.prp.2016.04.005","article-title":"Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms","volume":"212","author":"Bonsib","year":"2016","journal-title":"Pathol. Res. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI7319","article-title":"Tsc2+\/\u2212 mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background","volume":"104","author":"Onda","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/hmg\/3.10.1829","article-title":"9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene","volume":"3","author":"Carbonara","year":"1994","journal-title":"Hum. Mol. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/gcc.2870130411","article-title":"Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas","volume":"13","author":"Henske","year":"1995","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/ng0294-193","article-title":"Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients","volume":"6","author":"Green","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_20","first-page":"400","article-title":"Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions","volume":"59","author":"Henske","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","first-page":"1639","article-title":"Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors","volume":"151","author":"Henske","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1749-6632.1991.tb37755.x","article-title":"Pathology of tuberous sclerosis. Neuropathologic aspects","volume":"615","author":"Richardson","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1086\/321972","article-title":"Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions","volume":"69","author":"Niida","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/j.1750-3639.2010.00416.x","article-title":"Analysis of TSC cortical tubers by deep sequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events","volume":"20","author":"Qin","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1177\/15353702211038378","article-title":"Renal cystic disease in tuberous sclerosis complex","volume":"246","author":"Kumar","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1038\/onc.2015.358","article-title":"Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex","volume":"35","author":"Patel","year":"2016","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8639","DOI":"10.1007\/s11033-023-08624-w","article-title":"Biological function of Extracellular Vesicles (EVs): A review of the field","volume":"50","author":"Mohammadipoor","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6119","DOI":"10.1113\/jphysiol.2011.220277","article-title":"Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells","volume":"589","author":"Street","year":"2011","journal-title":"J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.gendis.2021.03.010","article-title":"Tsc2 mutation induces renal tubular cell nonautonomous disease","volume":"9","author":"Kumar","year":"2022","journal-title":"Genes Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kumar, P., Zadjali, F., Yao, Y., Siroky, B., Astrinidis, A., Gross, K.W., and Bissler, J.J. (2021). Tsc Gene Locus Disruption and Differences in Renal Epithelial Extracellular Vesicles. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.630933"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e12336","DOI":"10.1002\/jev2.12336","article-title":"Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers","volume":"12","author":"Bhaoighill","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zadjali, F., Kumar, P., Yao, Y., Johnson, D., Astrinidis, A., Vogel, P., Gross, K.W., and Bissler, J.J. (2020). Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051729"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Giannikou, K., Malinowska, I.A., Pugh, T.J., Yan, R., Tseng, Y.Y., Oh, C., Kim, J., Tyburczy, M.E., Chekaluk, Y., and Liu, Y. (2016). Whole Exome Sequencing Identifies TSC1\/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006242"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/sj.ejhg.5200484","article-title":"Loss of heterozygosity in renal and hepatic epithelial cystic cells from ADPKD1 patients","volume":"8","author":"Badenas","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1172\/JCI119147","article-title":"Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis","volume":"99","author":"Brasier","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ajpath.2022.10.007","article-title":"Identification of an Electrogenic 2Cl\u2212\/H+ Exchanger, ClC5, as a Chloride-Secreting Transporter Candidate in Kidney Cyst Epithelium in Tuberous Sclerosis","volume":"193","author":"Barone","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1903140","DOI":"10.1002\/advs.201903140","article-title":"Proteomic Identification Reveals the Role of Ciliary Extracellular-Like Vesicle in Cardiovascular Function","volume":"7","author":"Mohieldin","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1083\/jcb.11.1.248","article-title":"Cilia in different segments of the rat nephron","volume":"11","author":"Latta","year":"1961","journal-title":"J. Biophys. Biochem. Cytol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.ophtha.2012.03.020","article-title":"Tuberous sclerosis complex: Genotype\/phenotype correlation of retinal findings","volume":"119","author":"Aronow","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/sj.ejhg.5201402","article-title":"Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: Genotype\u2014Phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex","volume":"13","author":"Sancak","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","article-title":"A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells","volume":"11","author":"Kwiatkowski","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Carrella, S., Banfi, S., and Karali, M. (2020). Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.629158"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ncrna.2023.10.011","article-title":"Insight into the role of non-coding RNA in the diagnosis and treatment of retinitis pigmentosa","volume":"9","author":"Chen","year":"2024","journal-title":"Noncoding RNA Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41419-021-04386-0","article-title":"LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p","volume":"12","author":"Guo","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"G559","DOI":"10.1152\/ajpgi.00242.2017","article-title":"lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214","volume":"314","author":"Huang","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbrc.2018.05.146","article-title":"Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells","volume":"503","author":"Li","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","first-page":"12588","article-title":"LncRNA MIAT promotes the proliferation, migration, and invasion of melanoma cells through recruiting TCF12 and activating NFAT5","volume":"13","author":"Lu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13046-018-0725-3","article-title":"Long non-coding RNA MIAT promotes gastric cancer growth and metastasis through regulation of miR-141\/DDX5 pathway","volume":"37","author":"Sha","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3892\/etm.2021.9663","article-title":"Long non-coding RNA MIAT promotes the proliferation and invasion of laryngeal squamous cell carcinoma cells by sponging microRNA-613","volume":"21","author":"Song","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_51","first-page":"533","article-title":"Knockdown of lncRNA MIAT inhibits proliferation and cisplatin resistance in non-small cell lung cancer cells by increasing miR-184 expression","volume":"19","author":"Wu","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.7150\/ijbs.63488","article-title":"Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network","volume":"17","author":"Hao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13045-022-01235-1","article-title":"The long and short non-coding RNAs modulating EZH2 signaling in cancer","volume":"15","author":"Mirzaei","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ol.2020.12032","article-title":"Determination of long non-coding RNAs associated with EZH2 in neuroblastoma by RIP-seq, RNA-seq and ChIP-seq","volume":"20","author":"Ye","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/2211-5463.13579","article-title":"Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1","volume":"13","author":"Hong","year":"2023","journal-title":"FEBS Open Bio"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7305","DOI":"10.1038\/ncomms8305","article-title":"A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture","volume":"6","author":"Krol","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Wang, Z., Dai, R., and Ahmed, S.A. (2023). MicroRNA-183\/96\/182 cluster in immunity and autoimmunity. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134634"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.bbabio.2017.03.006","article-title":"Expression and putative role of mitochondrial transport proteins in cancer","volume":"1858","author":"Lytovchenko","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1172\/JCI122595","article-title":"Lipin 2\/3 phosphatidic acid phosphatases maintain phospholipid homeostasis to regulate chylomicron synthesis","volume":"129","author":"Zhang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1038\/s41467-019-09588-x","article-title":"Major vault protein suppresses obesity and atherosclerosis through inhibiting IKK-NF-kappaB signaling mediated inflammation","volume":"10","author":"Ben","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.18632\/oncotarget.2047","article-title":"nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer","volume":"5","author":"Lee","year":"2014","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Taube, M., Lisiak, N., Toton, E., and Rubis, B. (2024). Human Vault RNAs: Exploring Their Potential Role in Cellular Metabolism. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074072"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bai, H., Wang, C., Qi, Y., Xu, J., Li, N., Chen, L., Jiang, B., Zhu, X., Zhang, H., and Li, X. (2019). Major vault protein suppresses lung cancer cell proliferation by inhibiting STAT3 signaling pathway. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5665-6"},{"key":"ref_64","first-page":"920","article-title":"Major vault protein forms complexes with hypoxia-inducible factor (HIF)-1alpha and reduces HIF-1alpha level in ACHN human renal adenocarcinoma cells","volume":"101","author":"Iwashita","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zahedi, K., Barone, S., Brooks, M., Murray Stewart, T., Casero, R.A., and Soleimani, M. (2022). Renal Transcriptome and Metabolome in Mice with Principal Cell-Specific Ablation of the Tsc1 Gene: Derangements in Pathways Associated with Cell Metabolism, Growth and Acid Secretion. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810601"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Dowarha, D., Chou, R.H., and Yu, C. (2020). S100A1 blocks the interaction between p53 and mdm2 and decreases cell proliferation activity. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234152"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Nakagawa, M., Higuchi, S., Hashimura, M., Oguri, Y., Matsumoto, T., Yokoi, A., Ishibashi, Y., Ito, T., and Saegusa, M. (2022). Functional interaction between S100A1 and MDM2 may modulate p53 signaling in normal and malignant endometrial cells. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09249-1"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/cncy.21530","article-title":"HNF1beta and S100A1 are useful biomarkers for distinguishing renal oncocytoma and chromophobe renal cell carcinoma in FNA and core needle biopsies","volume":"123","author":"Conner","year":"2015","journal-title":"Cancer Cytopathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/j.1365-2559.2007.02655.x","article-title":"S100A1: A powerful marker to differentiate chromophobe renal cell carcinoma from renal oncocytoma","volume":"50","author":"Li","year":"2007","journal-title":"Histopathology"},{"key":"ref_70","first-page":"2041","article-title":"A conserved role of IQGAP1 in regulating TOR complex 1","volume":"125","author":"Tekletsadik","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chen, J.Q., Ou, Y.L., Huang, Z.P., Hong, Y.G., Tao, Y.P., Wang, Z.G., Ni, J.S., Hao, L.Q., and Lin, H. (2019). MicroRNA-212-3p inhibits the Proliferation and Invasion of Human Hepatocellular Carcinoma Cells by Suppressing CTGF expression. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-46088-w"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2147\/OTT.S114276","article-title":"miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells","volume":"11","author":"Tsai","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"95516","DOI":"10.18632\/oncotarget.20764","article-title":"Subependymal giant cell astrocytomas in Tuberous Sclerosis Complex have consistent TSC1\/TSC2 biallelic inactivation, and no BRAF mutations","volume":"8","author":"Bongaarts","year":"2017","journal-title":"Oncotarget"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s004390000390","article-title":"Molecular analysis of the TSC1 and TSC2 tumour suppressor genes in sporadic glial and glioneuronal tumours","volume":"107","author":"Parry","year":"2000","journal-title":"Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"102","DOI":"10.5414\/NP301008","article-title":"Astrocytic tumor with large cells and worrisome features in two patients with tuberous sclerosis: Drastically different diagnoses and prognoses","volume":"36","author":"Roux","year":"2017","journal-title":"Clin. Neuropathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100225","DOI":"10.1016\/j.xpro.2020.100225","article-title":"Extracellular vesicle and particle isolation from human and murine cell lines, tissues, and bodily fluids","volume":"2","author":"Bojmar","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"MacKenzie, M., Tigert, S., Lovato, D., Mir, H., Zahedi, K., Barone, S.L., Brooks, M., Soleimani, M., and Argyropoulos, C. (2022). To make a short story long: Simultaneous short and long RNA profiling on Nanopore devices. bioRxiv.","DOI":"10.1101\/2022.12.16.520507"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:55Z","timestamp":1760029495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":77,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073154"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073154","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}