{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:15:33Z","timestamp":1789924533684,"version":"4.0.1"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["13020251"],"award-info":[{"award-number":["13020251"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>CRISPR\/Cas9 is a recently discovered genomic editing technique that altered scientist\u2019s sight in studying genes function. Cas9 is controlled via guide (g) RNAs, which match the DNA targeted in cleavage to modify the respective gene. The development in prostate cancer (PC) modeling directed not only to novel resources for recognizing the signaling pathways overriding prostate cell carcinoma, but it has also created a vast reservoir for complementary tools to examine therapies counteracting this type of cancer. Various cultured somatic rat models for prostate cancer have been developed that nearly mimic human prostate cancer. Nano-medicine can passively target cancer cells via increasing bioavailability and conjugation via specific legend, contributing to reduced systemic side-effects and increased efficacy. This article highlights liposomal loaded Nano-medicine as a potential treatment for prostate cancer and clarifies the CRISPR\/Cas9 variation accompanied with prostate cancer. PC is induced experimentally in western rat model via ethinyl estradiol for 4 weeks and SC. dose of 3, 2\u2019- dimethyl-4-aminobiphenyl estradiol (DAE) (50mg\/kg) followed by treatment via targeted liposomal-coated compounds such as liposomal dexamethasone (DXM), liposomal doxorubicin (DOX) and liposomal Turmeric (TUR) (3mg\/kg IP) for four weeks in a comparative study to their non-targeted analogue dexamethasone, doxorubicin and Turmeric. 3, 2\u2019- dimethyl-4-aminobiphenylestradiol elicit prostate cancer in western rats within 5 months. Simultaneous supplementations with these liposomal compounds influence on prostate cancer; tumor markers were investigated via prostate-specific antigen (PSA), Nitric oxide (NOX) and CRISPR\/Cas9 gene editing. Several long non-coding RNAs were reported to be deregulated in prostate cell carcinoma, including <jats:italic>MALAT1<\/jats:italic>. On the other hand, gene expression of apoptotic biomarkers focal adhesion kinase (AKT-1), phosphatidylinistol kinase (PI3K) and glycogen synthase kinase-3 (GSK-3) was also investigated and further confirming these results via histopathological examination. Liposomal loaded dexamethasone; doxorubicin and Turmeric can be considered as promising therapeutic agents for prostate cancer via modulating CRISPR\/Cas9 gene editing and long non coding gene <jats:italic>MALAT1<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0302264","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:54:43Z","timestamp":1715277283000},"page":"e0302264","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["CRISPR-Cas9 genome and long non-coding RNAs as a novel diagnostic index for prostate cancer therapy via liposomal-coated compounds"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3920-6263","authenticated-orcid":true,"given":"Mai O.","family":"Kadry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab M.","family":"Abdel-Megeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"pone.0302264.ref001","first-page":"11","article-title":"Cancer statistics","volume":"63","author":"R Siegel","year":"2013","journal-title":"CA Cancer J Clin"},{"key":"pone.0302264.ref002","first-page":"436","volume":"454","author":"A Mantovani","year":"2008","journal-title":"Cancer-related inflammation. Nature"},{"key":"pone.0302264.ref003","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.1158\/0008-5472.CAN-12-3228","article-title":"Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4 -STAT3 signaling","volume":"73","author":"LY Fang","year":"2013","journal-title":"Cancer Res"},{"key":"pone.0302264.ref004","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/labinvest.2013.69","article-title":"M2-polarized tumor-associated macrophages promoted epithelial- mesenchymal transition in pancreatic cancer cells, partially through TLR4\/IL-10 signaling pathway","volume":"93","author":"CY Liu","year":"2013","journal-title":"Lab Invest"},{"key":"pone.0302264.ref005","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/imm.12023","article-title":"Anti-tumor strategies aiming to target tumor-associated macrophages","volume":"138","author":"X Tang","year":"2013","journal-title":"Immunol"},{"key":"pone.0302264.ref006","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMra050541","article-title":"Anti-inflammatory action of glucocorticoids\u2013new mechanisms for old drugs","volume":"353","author":"T Rhen","year":"2005","journal-title":"N Engl J Med"},{"key":"pone.0302264.ref007","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1593\/neo.04340","article-title":"Liposome-encapsulated prednisolone phosphate inhibits growth of established tumors in mice","volume":"7","author":"RM Schiffelers","year":"2005","journal-title":"Neoplasia"},{"issue":"1","key":"pone.0302264.ref008","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.canlet.2008.03.025","article-title":"Turmeric and cancer: an \u201cold-age\u201d disease with an \u201cage-old\u201d solution","volume":"267","author":"P Anand","year":"2008","journal-title":"Cancer Lett"},{"key":"pone.0302264.ref009","first-page":"3521","article-title":"Co-delivery of Turmeric and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with prostate cancer","volume":"8","author":"BL Wang","year":"2013","journal-title":"Int J Nanomedicine"},{"key":"pone.0302264.ref010","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jconrel.2011.09.063","article-title":"Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress","volume":"161","author":"T Lammers","year":"2012","journal-title":"J Control Release"},{"key":"pone.0302264.ref011","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s40259-013-0070-1","article-title":"Pegylated liposomal doxorubicin: a guide to its use in various malignancies","volume":"27","author":"KA Lyseng-Williamson","year":"2013","journal-title":"BioDrugs"},{"key":"pone.0302264.ref012","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1023\/A:1016225024121","article-title":"A phase II study of caelyx (liposomal doxorubicin) in metastatic carcinoma of the prostate: tolerability and efficacy modification by liposomal encapsulation","volume":"20","author":"R McMenemin","year":"2002","journal-title":"Invest New Drugs"},{"key":"pone.0302264.ref013","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.ctrv.2013.10.005","article-title":"Liposomal nanomedicines in the treatment of prostate cancer","volume":"40","author":"J Kroon","year":"2014","journal-title":"Cancer Treat Rev"},{"key":"pone.0302264.ref014","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1002\/art.11140","article-title":"Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes","volume":"48","author":"JM Metselaar","year":"2003","journal-title":"Arthrit. Rheum"},{"key":"pone.0302264.ref015","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/08982100801893978","article-title":"Utility of targeted glucocorticoids in cancer therapy","volume":"18","author":"M Banciu","year":"2008","journal-title":"J Liposome Res"},{"key":"pone.0302264.ref016","first-page":"300","article-title":"Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth In Vivo","volume":"22","author":"Jan Kroon","year":"2015","journal-title":"The prost"},{"issue":"3","key":"pone.0302264.ref017","first-page":"203","article-title":"Nuclear factor-kappaB: the enemy within","volume":"6","author":"BB Aggarwal","year":"2004","journal-title":"Cancer Cell"},{"issue":"4","key":"pone.0302264.ref018","first-page":"129","article-title":"Multi-edged sword against cancer: ancient exotic spice","volume":"68","author":"S Chakraborty","year":"2014","journal-title":"Indian J Physiol Allied Sci"},{"key":"pone.0302264.ref019","article-title":"Anti-cancer effects of Turmeric: cycle of life and death","volume":"3","author":"G Sa","year":"2014","journal-title":"Cell Div"},{"key":"pone.0302264.ref020","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0005-2736(91)90246-5","article-title":"Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo","volume":"1066","author":"T.M. Allen","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"pone.0302264.ref021","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1146\/annurev.anchem.1.031207.112747","article-title":"Liposomes: Technologies and analytical applications. Annu","volume":"1","author":"A. Jesorka","year":"2008","journal-title":"Rev. Anal. Chem"},{"issue":"1","key":"pone.0302264.ref022","first-page":"2","article-title":"GE11 Peptide as an Active Targeting Agent in Antitumor Therapy: A Minireview","volume":"10","author":"G. Ida","year":"2018","journal-title":"Pharmaceutics"},{"key":"pone.0302264.ref023","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1476-4598-6-24","article-title":"The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention","volume":"6","author":"PA John","year":"2007","journal-title":"Mol Cancer"},{"issue":"2","key":"pone.0302264.ref024","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbrc.2005.06.093","article-title":"Turmeric inhibits interferon-alpha induced NF-kappaB and COX-2 in human A549 non-small cell prostate cancer cells","volume":"334","author":"J Lee","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"issue":"23","key":"pone.0302264.ref025","first-page":"5975","article-title":"DD3: a new prostate-specific gene, highly overexpressed in prostate cancer","volume":"59","author":"MJ Bussemakers","year":"1999","journal-title":"Cancer Res"},{"key":"pone.0302264.ref026","first-page":"4987103","article-title":"Long Noncoding RNAs as Biomarkers in Cancer","author":"Luka Bolha","year":"2018","journal-title":"Epigenetic Biomarkers in Cancer"},{"key":"pone.0302264.ref027","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"NE Sanjana","year":"2014","journal-title":"Nat Methods"},{"key":"pone.0302264.ref028","first-page":"766","volume-title":"Theory and Practice of Histological Techniques","author":"JD Bancroft","year":"1996","edition":"4"},{"key":"pone.0302264.ref029","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1096\/fj.08-106468","article-title":"andMuise-Helmericks, R. C. VEGF stimulation of mitochondrial biogenesis: requirement of Akt3 kinase","volume":"22","author":"G. L. Wright","year":"2008","journal-title":"FASEB J"},{"key":"pone.0302264.ref030","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4161\/cc.5.6.2561","article-title":"Akt\/PKB signaling in cancer: a function in cell motility and invasion","volume":"5","author":"M. Yoeli-Lerner","year":"2006","journal-title":"C. Cycle"},{"key":"pone.0302264.ref031","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2174\/156800908784293659","article-title":"The PTEN\/PI3K\/Akt signaling pathway in cancer, therapeutic implications","volume":"8","author":"A. Carnero","year":"2008","journal-title":"Curr. Canc. D. Tar"},{"key":"pone.0302264.ref032","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/156800908783497159","article-title":"Advances of Akt pathway in human oncogenesis and as a target for anti-cancer drug discovery","volume":"8","author":"G. Z. Cheng","year":"2008","journal-title":"Curr. Canc. D. Tar"},{"key":"pone.0302264.ref033","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1242\/dev.01864","article-title":"Essential role of protein kinase B\u03b3 (PKB\u03b3\/Akt3) in postnatal brain development but not in glucose homeostasis","volume":"132","author":"O. Tschopp","year":"2005","journal-title":"Development"},{"key":"pone.0302264.ref034","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.bbrc.2003.09.132","article-title":"Role of PI3K\/Akt\/mTOR signaling in the cell cycle progression of human prostate cancer","volume":"310","author":"N. Gao","year":"2003","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"pone.0302264.ref035","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1002\/ijc.23261","article-title":"Interleukin-6 activatesPI3K\/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival","volume":"122","author":"B. Wegiel","year":"2008","journal-title":"Int. J. Cancer"},{"key":"pone.0302264.ref036","first-page":"1801","article-title":"\u03b2-Catenin-related anomalies in apoptosis-resistant and hormone-refractory prostate cancer cells","volume":"9","author":"A. de la Taille","year":"2003","journal-title":"Clin. Cancer Res"},{"key":"pone.0302264.ref037","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.4161\/cc.6.16.4603","article-title":"Tuning cell cycle regulation with aniron key","volume":"6","author":"Y. Yu","year":"2007","journal-title":"C. Cycle"},{"issue":"R1","key":"pone.0302264.ref038","doi-asserted-by":"crossref","first-page":"R40","DOI":"10.1093\/hmg\/ddu125","article-title":"CRISPR\/Cas9 for genome editing: progress, implications and challenges","volume":"23","author":"F Zhang","year":"2014","journal-title":"H. Mol.Genet"},{"issue":"6","key":"pone.0302264.ref039","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"PD Hsu","year":"2014","journal-title":"Cell"},{"key":"pone.0302264.ref040","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41585-020-0302-3","article-title":"CRISPR\u2013Cas9 ER\u03b2 deletion reveals roles in prostate","volume":"17","author":"Fenner Annette","year":"2020","journal-title":"Nat. Rev. Urology"},{"key":"pone.0302264.ref041","doi-asserted-by":"crossref","first-page":"6130","DOI":"10.1158\/0008-5472.CAN-07-0533","article-title":"MicroRNA expression profiling in prostate cancer","volume":"167","author":"KP Porkka","year":"2007","journal-title":"Cancer Res"},{"key":"pone.0302264.ref042","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.med.59.053006.104707","article-title":"Micro RNAs in Cancer","volume":"60","author":"R Garzon","year":"2009","journal-title":"Annu Rev Med"},{"issue":"2","key":"pone.0302264.ref043","first-page":"281","article-title":"Micro RNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"DP Bartel","year":"2004","journal-title":"Cell"},{"key":"pone.0302264.ref044","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1002\/jcb.26445","article-title":"The potential of micro RNAs as human prostate cancer biomarkers: A meta-analysis of related studies","volume":"119","author":"CJ Song","year":"2018","journal-title":"J Cell Biochem"},{"issue":"8","key":"pone.0302264.ref045","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/emmm.201100154","article-title":"A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage prostate cancer","volume":"3","author":"F Bianchi","year":"2011","journal-title":"EMBO Mol Med"},{"issue":"3","key":"pone.0302264.ref046","doi-asserted-by":"crossref","first-page":"e4995","DOI":"10.1371\/journal.pone.0004995","article-title":"New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression","volume":"4","author":"RA Clarke","year":"2009","journal-title":"PLoS One"},{"issue":"3","key":"pone.0302264.ref047","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s13277-013-0739-6","article-title":"PCA3 in the detection and management of early prostate cancer","volume":"34","author":"X Filella","year":"2013","journal-title":"Tumor Biol"},{"issue":"2","key":"pone.0302264.ref048","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.bbrc.2005.12.014","article-title":"Turmeric induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia","volume":"340","author":"J Rajasingh","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0302264.ref049","first-page":"1025","article-title":"Intratumoral immune landscape: immunogenicity to tolerogenicity","volume":"2","author":"AK Panda","year":"2015","journal-title":"Austin J Clin Immunol"},{"issue":"1\u20132","key":"pone.0302264.ref050","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11010-009-0269-0","article-title":"Multifocal signal modulation therapy of cancer: ancient weapon, modern targets","volume":"336","author":"T Das","year":"2010","journal-title":"Mol Cell Biochem"},{"key":"pone.0302264.ref051","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13008-015-0012-z","article-title":"Turmeric and tumor immune-editing: resurrecting the immune system","volume":"10","author":"S Bose","year":"2015","journal-title":"Cell Div"},{"issue":"3","key":"pone.0302264.ref052","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/carcin\/bgv006","article-title":"Turmeric mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer","volume":"36","author":"S Toden","year":"2015","journal-title":"Carcinogenesis"},{"issue":"7","key":"pone.0302264.ref053","first-page":"2567","article-title":"Death by design: where Turmeric sensitizes drug-resistant tumors","volume":"32","author":"S Saha","year":"2012","journal-title":"Anticancer Res"},{"key":"pone.0302264.ref054","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1186\/1556-276X-6-482","article-title":"Nanoliposomes for encapsulation and delivery of the potential antitumoral methyl 6-methoxy-3- (4-methoxyphenyl)-1H-indole-2-carboxylate","volume":"6","author":"A.S. Abreu","year":"2011","journal-title":"Nanoscale Res. Lett"},{"key":"pone.0302264.ref055","first-page":"275","article-title":"Nanotechnology and Drug Delivery Part 2: Nanostructures for Drug Delivery","volume":"8","author":"N.A. Ochekpe","year":"2009","journal-title":"Trop. J. Pharm. Res"},{"key":"pone.0302264.ref056","first-page":"3","article-title":"Nanoliposome Potentials in Nanotherapy: A Concise Overview. Int","volume":"6","author":"K. Khosravi-Darani","year":"2010","journal-title":"J. Nanosci. Nanotechnol"},{"key":"pone.0302264.ref057","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/08982100802465941","article-title":"Nanoliposomes and their applications in food nanotechnology","volume":"18","author":"M.R. Mozafari","year":"2008","journal-title":"J. Liposome Res"},{"key":"pone.0302264.ref058","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0378-5173(02)00217-X","article-title":"Marinosomes, marine lipid-based liposomes: physical characterization and potential application in cosmetics","volume":"242","author":"N. Moussaoui","year":"2002","journal-title":"Int. J. 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