{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:37:35Z","timestamp":1780468655972,"version":"3.54.1"},"reference-count":81,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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>Ovarian cancer (OC) remains the leading cause of death among gynecologic cancers. Most women diagnosed with OC at advanced stages eventually develop relapse and chemoresistance, leading to poor clinical outcomes. While piRNAs have emerged as critical regulators of gene expression and tumor biology, their specific roles in OC remain to be fully elucidated. This study integrated clinical and computational analyses to investigate the expression pattern and functional relevance of P-element-induced wimpy testis (PIWI)-interacting RNA-823 (piR-823) and its associated protein piwi-like RNA-mediated gene silencing 1 (PIWIL1)\/DNA methyltransferase 3B (DNMT3B)\/E-cadherin (CDH1) axis in OC tissues from 40 patients, with 20 non-cancer control samples. Expression profiling was performed using qPCR on OC and normal ovarian tissues, followed by correlation and regression analyses. Public databases, including GEPIA, TNM plot, and MethBank, were explored to validate gene expression, methylation status, and pathway enrichment. Our results revealed that piR-823, PIWIL1, and DNMT3B were significantly upregulated in OC tissues (p &lt; 0.001, p = 0.009, and p &lt; 0.001, respectively), and they correlated positively with each other and inversely with CDH1 expression. CDH2, OCT4, and NANOG were significantly upregulated (p = 0.011, p = 0.03, and p &lt; 0.001, respectively), whereas CDH1 expression was significantly downregulated (p &lt; 0.001) in OC tissues. In silico analyses supported DNMT3B-mediated CDH1 promoter methylation, epithelial\u2013mesenchymal transition (EMT), and stemness pathway enrichment. Our integrated computational and clinical analyses indicate that the piR-823\/PIWIL1\/DNMT3B\/CDH1 axis is a putative epigenetic regulator of EMT and cancer stemness in ovarian cancer. Additionally, piR-823 may serve as a promising prognostic biomarker and therapeutic target, offering novel insights into OC pathogenesis and treatment.<\/jats:p>","DOI":"10.3390\/ijms27020823","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"823","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["P-Element-Induced Wimpy Testis (PIWI)-Interacting RNA-823\/PIWIL1\/DNMT3B\/CDH1 as Potential Axis to Drive EMT, Stemness, and Tumor Aggressiveness in Ovarian Cancer Tissue Samples: An Integrative Computational and Clinical Insights"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0586-2147","authenticated-orcid":false,"given":"Fatma H.","family":"Shaker","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5406-2029","authenticated-orcid":false,"given":"Eman F.","family":"Sanad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9327-286X","authenticated-orcid":false,"given":"Hesham","family":"Elghazaly","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-2618","authenticated-orcid":false,"given":"Shih-Min","family":"Hsia","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"School of Food Safety, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"Nutrition Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan"},{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan"},{"name":"TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-107X","authenticated-orcid":false,"given":"Nadia M.","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15330338241249692","DOI":"10.1177\/15330338241249692","article-title":"piR-1919609 Is an Ideal Potential Target for Reversing Platinum Resistance in Ovarian Cancer","volume":"23","author":"Yan","year":"2024","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/s41419-022-04976-6","article-title":"Ascitic fluid shear stress in concert with hepatocyte growth factor drive stemness and chemoresistance of ovarian cancer cells via the c-Met-PI3K\/Akt-miR-199a-3p signaling pathway","volume":"13","author":"Hassan","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.ijbiomac.2018.06.036","article-title":"Origins based clinical and molecular complexities of epithelial ovarian cancer","volume":"118","author":"Muinao","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"viii51","DOI":"10.1093\/annonc\/mdx441","article-title":"Treatment of recurrent ovarian cancer","volume":"28","author":"Pignata","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Reid, B.M., and Fridley, B.L. (2020). DNA Methylation in Ovarian Cancer Susceptibility. Cancers, 13.","DOI":"10.3390\/cancers13010108"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13048-022-01002-3","article-title":"Role of different non-coding RNAs as ovarian cancer biomarkers","volume":"15","author":"Beg","year":"2022","journal-title":"J. Ovarian Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.semcancer.2021.03.038","article-title":"The hallmarks of ovarian cancer stem cells and niches: Exploring their harmonious interplay in therapy resistance","volume":"77","author":"Motohara","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1757-2215-7-76","article-title":"The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer","volume":"7","author":"Takai","year":"2014","journal-title":"J. Ovarian Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121997","DOI":"10.1016\/j.lfs.2023.121997","article-title":"Remodeled tumor immune microenvironment (TIME) parade via natural killer cells reprogramming in breast cancer","volume":"330","author":"Elanany","year":"2023","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nowicki, A., Kulus, M., Wieczorkiewicz, M., Pie\u0144kowski, W., Stefa\u0144ska, K., Skupin-Mrugalska, P., Bryl, R., Mozdziak, P., Kempisty, B., and Piotrowska-Kempisty, H. (2021). Ovarian Cancer and Cancer Stem Cells\u2014Cellular and Molecular Characteristics, Signaling Pathways, and Usefulness as a Diagnostic Tool in Medicine and Oncology. Cancers, 13.","DOI":"10.3390\/cancers13164178"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1038\/s41388-018-0637-x","article-title":"An evolving story of the metastatic voyage of ovarian cancer cells: Cellular and molecular orchestration of the adipose-rich metastatic microenvironment","volume":"38","author":"Motohara","year":"2019","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10585-021-10077-z","article-title":"TGF\u03b2 signaling networks in ovarian cancer progression and plasticity","volume":"38","author":"Kumari","year":"2021","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.2183\/pjab.96.003","article-title":"The piRNA pathway in Drosophila ovarian germ and somatic cells","volume":"96","author":"Sato","year":"2020","journal-title":"Proc. Jpn. Acad. Ser. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40364-024-00563-3","article-title":"Critical appraisal of the piRNA-PIWI axis in cancer and cancer stem cells","volume":"12","author":"Siegl","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"188772","DOI":"10.1016\/j.bbcan.2022.188772","article-title":"Emerging roles of PIWI-interacting RNAs (piRNAs) and PIWI proteins in head and neck cancer and their potential clinical implications","volume":"1877","author":"Chattopadhyay","year":"2022","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10555-020-09863-0","article-title":"piRNAs: Biogenesis and their potential roles in cancer","volume":"39","author":"Guo","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2217\/epi.15.37","article-title":"The role of piRNA and its potential clinical implications in cancer","volume":"7","author":"Calcagno","year":"2015","journal-title":"Epigenomics"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ding, X., Li, Y., L\u00fc, J., Zhao, Q., Guo, Y., Lu, Z., Ma, W., Liu, P., Pestell, R.G., and Liang, C. (2021). piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association with Luminal Breast Cancer. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.641052"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1111\/cas.13300","article-title":"piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1","volume":"108","author":"Yin","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9028","DOI":"10.1111\/jcmm.15537","article-title":"Novel evidence for oncogenic piRNA-823 as a promising prognostic biomarker and a potential therapeutic target in colorectal cancer","volume":"24","author":"Feng","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.canlet.2011.10.004","article-title":"piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells","volume":"315","author":"Cheng","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"152848","DOI":"10.1016\/j.prp.2020.152848","article-title":"piR-823 demonstrates tumor oncogenic activity in esophageal squamous cell carcinoma through DNA methylation induction via DNA methyltransferase 3B","volume":"216","author":"Su","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6419","DOI":"10.21873\/anticanres.11239","article-title":"Expression Levels of PIWI-interacting RNA, piR-823, Are Deregulated in Tumor Tissue, Blood Serum and Urine of Patients with Renal Cell Carcinoma","volume":"36","author":"Iliev","year":"2016","journal-title":"Anticancer. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2147\/OTT.S91295","article-title":"Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients","volume":"9","author":"Slaby","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/leu.2014.135","article-title":"piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma","volume":"29","author":"Yan","year":"2015","journal-title":"Leukemia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1038\/s41388-019-0788-4","article-title":"piRNA-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment","volume":"38","author":"Li","year":"2019","journal-title":"Oncogene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23668","DOI":"10.18632\/aging.103820","article-title":"DNMT3B silencing suppresses migration and invasion by epigenetically promoting miR-34a in bladder cancer","volume":"12","author":"Xu","year":"2020","journal-title":"Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.lfs.2008.06.019","article-title":"Epigenetic alterations of CDH1 and APC genes: Relationship with activation of Wnt\/\u03b2-catenin Pathway in invasive ductal carcinoma of breast","volume":"83","author":"Prasad","year":"2008","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.1038\/onc.2016.180","article-title":"DNA methylation by DNMT1 and DNMT3b methyltransferases is driven by the MUC1-C oncoprotein in human carcinoma cells","volume":"35","author":"Rajabi","year":"2016","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100701","DOI":"10.1016\/j.repbio.2022.100701","article-title":"DNMT3B attenuated the inhibition of TET3 on epithelial-mesenchymal transition in TGF-\u03b21-induced ovarian cancer by methylating the TET3 promoter","volume":"22","author":"Ye","year":"2022","journal-title":"Reprod. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Papakonstantinou, E., Pappa, I., Androutsopoulos, G., Adonakis, G., Maroulis, I., and Tzelepi, V. (2023). Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma. Cancers, 15.","DOI":"10.20944\/preprints202308.1193.v1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2012.10.023","article-title":"Ovarian cancer stem cells: Working towards the root of stemness","volume":"338","author":"Foster","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Teeuwssen, M., and Fodde, R. (2019). Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101658"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.ygyno.2013.09.034","article-title":"The Wnt\/\u03b2-Catenin Pathway in Ovarian Cancer: A Review","volume":"131","author":"Arend","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41698-025-00840-w","article-title":"piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer","volume":"9","author":"Qin","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_36","first-page":"339","article-title":"PIWI Interacting RNA-823: Epigenetic Regulator of The Triple Negative Breast Cancer Cells Proliferation","volume":"6","author":"Oner","year":"2022","journal-title":"Eurasian J. Med. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sabbah, N.A., Abdalla, W.M., Mawla, W.A., AbdAlMonem, N., Gharib, A.F., Abdul-Saboor, A., Abdelazem, A.S., and Raafat, N. (2021). piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients. Genes, 12.","DOI":"10.3390\/genes12040598"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41419-022-04922-6","article-title":"piR-823 inhibits cell apoptosis via modulating mitophagy by binding to PINK1 in colorectal cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9151","DOI":"10.12659\/MSM.914222","article-title":"The Combination of piR-823 and Eukaryotic Initiation Factor 3 B (EIF3B) Activates Hepatic Stellate Cells via Upregulating TGF-\u03b21 in Liver Fibrogenesis","volume":"24","author":"Tang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54650","DOI":"10.18632\/oncotarget.10567","article-title":"Specific patterns of PIWI-interacting small noncoding RNA expression in dysplastic liver nodules and hepatocellular carcinoma","volume":"7","author":"Rizzo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/j.clinbiochem.2011.06.004","article-title":"Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers","volume":"44","author":"Cui","year":"2011","journal-title":"Clin. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"888","DOI":"10.21873\/cgp.20545","article-title":"Circulating Serum piRNAs as Diagnostic and Prognostic Tools for Clear Cell Renal Cell Carcinoma","volume":"22","author":"Kasik","year":"2025","journal-title":"Cancer Genom. Proteom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00210-024-03308-z","article-title":"piR-823 tale as emerging cancer-hallmark molecular marker in different cancer types: A step-toward ncRNA-precision","volume":"398","author":"Shaker","year":"2024","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12943-018-0767-3","article-title":"Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer","volume":"17","author":"Weng","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Liman\u00f3wka, P., Ochman, B., and \u015awi\u0119tochowska, E. (2023). PiRNA Obtained through Liquid Biopsy as a Possible Cancer Biomarker. Diagnostics, 13.","DOI":"10.3390\/diagnostics13111895"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9932","DOI":"10.18632\/aging.102417","article-title":"Emerging roles of piRNAs in cancer: Challenges and prospects","volume":"11","author":"Cheng","year":"2019","journal-title":"Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13045-015-0133-5","article-title":"piRNA involvement in genome stability and human cancer","volume":"8","author":"Moyano","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.7150\/ijbs.68221","article-title":"The regulatory function of piRNA\/PIWI complex in cancer and other human diseases: The role of DNA methylation","volume":"18","author":"Jia","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s12943-019-1052-9","article-title":"The emerging role of the piRNA\/piwi complex in cancer","volume":"18","author":"Liu","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1134\/S1068162014030169","article-title":"piRNA biogenesis and its functions","volume":"40","author":"Huang","year":"2014","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12943-019-1011-5","article-title":"Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation","volume":"18","author":"Ai","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107328","DOI":"10.1016\/j.phrs.2024.107328","article-title":"Non-nucleoside inhibitors of DNMT1 and DNMT3 for targeted cancer therapy","volume":"207","author":"Chen","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1158\/1541-7786.MCR-10-0568","article-title":"Mechanism of the Mesenchymal\u2013Epithelial Transition and Its Relationship with Metastatic Tumor Formation","volume":"9","author":"Yao","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.molonc.2016.04.002","article-title":"Gene expression profiling of single circulating tumor cells in ovarian cancer\u2014Establishment of a multi-marker gene panel","volume":"10","author":"Blassl","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"189346","DOI":"10.1016\/j.bbcan.2025.189346","article-title":"Deciphering the \u2018Rosetta Stone\u2019 of ovarian cancer stem cells: Opportunities and challenges","volume":"1880","author":"Tan","year":"2025","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Rev. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sohn, E.J. (2022). PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09807-7"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s13046-024-03243-0","article-title":"SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2\/p-EphA2 Axis","volume":"43","author":"E","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1158\/1541-7786.MCR-21-0887","article-title":"DNA Methyltransferase 3B\u2013Mediated Intratumoral Heterogeneity and Therapeutic Targeting in Breast Cancer Recurrence and Metastasis","volume":"20","author":"So","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13048-019-0596-z","article-title":"Wnt\/\u03b2-Catenin Signalling in Ovarian Cancer: Insights into Its Hyperactivation and Function in Tumorigenesis","volume":"12","author":"Nguyen","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cellsig.2018.03.014","article-title":"Inhibition of DNMT suppresses the stemness of colorectal cancer cells through down-regulating Wnt signaling pathway","volume":"47","author":"Li","year":"2018","journal-title":"Cell Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102031","DOI":"10.1016\/j.omtn.2023.102031","article-title":"Nimbolide-based nanomedicine inhibits breast cancer stem-like cells by epigenetic reprogramming of DNMTs-SFRP1-Wnt\/\u03b2-catenin signaling axis","volume":"34","author":"Mohapatra","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"096368972096916","DOI":"10.1177\/0963689720969167","article-title":"Characteristics of TGFBR1\u2013EGFR\u2013CTNNB1\u2013CDH1 Signaling Axis in Wnt-Regulated Invasion and Migration in Lung Cancer","volume":"29","author":"Liu","year":"2020","journal-title":"Cell Transplant."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"69538","DOI":"10.18632\/oncotarget.18422","article-title":"MiR-23a promotes TGF-\u03b21-induced EMT and tumor metastasis in breast cancer cells by directly targeting CDH1 and activating Wnt\/\u03b2-catenin signaling","volume":"8","author":"Ma","year":"2017","journal-title":"Oncotarget"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12929-014-0073-3","article-title":"Promoter methylation analysis of WNT\/\u03b2-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer","volume":"21","author":"Samaei","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.omtn.2021.06.002","article-title":"EFNA4 promotes cell proliferation and tumor metastasis in hepatocellular carcinoma through a PIK3R2\/GSK3\u03b2\/\u03b2-catenin positive feedback loop","volume":"25","author":"Lin","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1080\/15548627.2025.2485420","article-title":"EPG-5 regulates TGFB\/TGF-\u03b2 and WNT signalling by modulating retrograde endocytic trafficking","volume":"21","author":"Yuan","year":"2025","journal-title":"Autophagy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1089\/gtmb.2022.0113","article-title":"P-Element-Induced Wimpy Testis Proteins and P-Element-Induced Wimpy Testis-Interacting RNAs Expression in Ovarian Cancer Stem Cells","volume":"27","author":"Sohn","year":"2023","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41392-021-00485-8","article-title":"PIWIL1 governs the crosstalk of cancer cell metabolism and immunosuppressive microenvironment in hepatocellular carcinoma","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Liu, S., Yan, Y., Cui, Z., Feng, H., Zhong, F., Liu, Z., Li, Y., Ou, X., and Li, W. (2023). Relationship between PIWIL1 gene polymorphisms and epithelial ovarian cancer susceptibility among southern Chinese woman: A three-center case\u2013control study. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11651-2"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chen, Z., Che, Q., He, X., Wang, F., Wang, H., Zhu, M., Sun, J., and Wan, X. (2015). Stem cell protein Piwil1 endowed endometrial cancer cells with stem-like properties via inducing epithelial-mesenchymal transition. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1794-8"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3802\/jgo.2015.26.2.87","article-title":"FIGO\u2019s staging classification for cancer of the ovary, fallopian tube, and peritoneum: Abridged republication","volume":"26","author":"Prat","year":"2015","journal-title":"J. Gynecol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00592-012-0373-6","article-title":"Effect of obesity and glycemic control on serum lipocalins and insulin-like growth factor axis in type 2 diabetic patients","volume":"50","author":"Hamdy","year":"2013","journal-title":"Acta Diabetol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3109\/00365513.2012.723135","article-title":"Serum retinol binding protein-4 and neutrophil gelatinase-associated lipocalin are interrelated in pancreatic cancer patients","volume":"72","author":"Hamdy","year":"2012","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/MPA.0b013e3182550d9d","article-title":"Clinical value of circulating lipocalins and insulin-like growth factor axis in pancreatic cancer diagnosis","volume":"42","author":"Hamdy","year":"2013","journal-title":"Pancreas"},{"key":"ref_75","first-page":"73635","article-title":"Evaluation of C-reactive protein, endothelin-1, adhesion molecule(s), and lipids as inflammatory markers in type 2 diabetes mellitus patients","volume":"2007","author":"Suwailem","year":"2007","journal-title":"Mediat. Inflamm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/jir.2013.0059","article-title":"The serine protease granzyme B as an inflammatory marker, in relation to the insulin receptor cleavage in human obesity and type 2 diabetes mellitus","volume":"34","author":"Hamdy","year":"2014","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mad.2018.03.009","article-title":"PIWI-piRNA pathway: Setting the pace of aging by reducing DNA damage","volume":"173","author":"Lenart","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_78","first-page":"4347","article-title":"Diagnostic value of urinary molecular markers in bladder cancer","volume":"23","author":"Eissa","year":"2003","journal-title":"Anticancer. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"154570","DOI":"10.1016\/j.prp.2023.154570","article-title":"LncRNA NNT-AS1\/hsa-miR-485-5p\/HSP90 axis in-silico and clinical prospect correlated-to histologic grades-based CRC stratification: A step toward ncRNA Precision","volume":"247","author":"Abulsoud","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"619","DOI":"10.3233\/CBM-160603","article-title":"Beclin-1 and hypoxia-inducible factor-1\u03b1 genes expression: Potential biomarkers in acute leukemia patients","volume":"16","author":"Radwan","year":"2016","journal-title":"Cancer Biomark."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"106427","DOI":"10.1016\/j.bioorg.2023.106427","article-title":"New trends in synthetic drugs and natural products targeting 20S proteasomes in cancers","volume":"133","author":"Atta","year":"2023","journal-title":"Bioorganic Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/823\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:05:06Z","timestamp":1768388706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":81,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020823"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020823","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]}}}