{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:56:45Z","timestamp":1779119805291,"version":"3.51.4"},"reference-count":42,"publisher":"Termedia Sp. z.o.o.","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cent Eur J Immunol"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Aim of\u00a0the\u00a0study was to investigate the\u00a0roles and interaction mechanisms of\u00a0RAB40C and SNX9 in prostate adenocarcinoma (PRAD) progression and their impact on the\u00a0Hippo signaling pathway. PRAD is a\u00a0significant health concern, and understanding the\u00a0molecular underpinnings is essential for its effective management. Objective of\u00a0this study was to identify key genes and pathways involved in PRAD using weighted gene co-expression network analysis (WGCNA) and determine the\u00a0functional implications of\u00a0RAB40C and its relationship with SNX9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>WGCNA was used to chart gene co-expression patterns in PRAD. Functional enrichment analyses of\u00a0significant modules were performed, and prognostic insights were derived through differential gene expression analysis. The\u00a0interaction between RAB40C and SNX9 was elucidated using various in vitro assays and databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WGCNA identified a\u00a0module (MEblue) highly correlated with PRAD. The\u00a0hub gene was revealed, with RAB40C being central to PRAD progression. The\u00a0knockdown of\u00a0RAB40C inhibited PRAD cell proliferation, migration, and invasion. SNX9 was identified as a\u00a0substrate protein interacting with RAB40C. The\u00a0silencing of\u00a0RAB40C led to increased SNX9 expression, suggesting an inverse regulatory relationship. RAB40C promoted SNX9 degradation via the\u00a0ubiquitin-proteasome pathway. Silencing RAB40C reduced PRAD cell proliferation, migration, and invasion, effects that were counteracted by simultaneous SNX9 suppression. The\u00a0interaction between RAB40C and SNX9 influenced target proteins of\u00a0the\u00a0Hippo signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RAB40C is essential for the\u00a0progression of\u00a0PRAD, partly through modulating SNX9 levels and the\u00a0Hippo signaling pathway. This interplay offers novel insights for PRAD therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5114\/ceji.2025.156367","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:48:11Z","timestamp":1769158091000},"source":"Crossref","is-referenced-by-count":1,"title":["RAB40C regulates SNX9 stability via the\u00a0ubiquitin-proteasome system and modulates the\u00a0Hippo signaling pathway of\u00a0prostate adenocarcinoma"],"prefix":"10.5114","author":[{"given":"Liang","family":"Qin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuwei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuifeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3061","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref-1655920","doi-asserted-by":"crossref","unstructured":"Madueke I, Hu WY, Hu D, et al. (2019): The\u00a0role of\u00a0WNT10B in normal prostate gland development and prostate cancer. Prostate 79: 1692-1704.","DOI":"10.1002\/pros.23894"},{"key":"ref-1655921","doi-asserted-by":"crossref","unstructured":"Pernar CH, Ebot EM, Wilson KM, Mucci LA (2018): The\u00a0epidemiology of\u00a0prostate cancer. Cold Spring Harbor Perspect Med 8: a030361.","DOI":"10.1101\/cshperspect.a030361"},{"key":"ref-1655922","doi-asserted-by":"crossref","unstructured":"Smith MR, Saad F, Chowdhury S, et al. (2021): Apalutamide and overall survival in prostate cancer. Eur Urol 79: 150-158.","DOI":"10.1016\/j.eururo.2020.08.011"},{"key":"ref-1655923","doi-asserted-by":"crossref","unstructured":"Kucera R, Pecen L, Topolcan O, et al. (2020): Prostate cancer management: long-term beliefs, epidemic developments in the\u00a0early twenty-first century and 3PM dimensional solutions. EPMA J 11: 399-418.","DOI":"10.1007\/s13167-020-00214-1"},{"key":"ref-1655924","doi-asserted-by":"crossref","unstructured":"Kumar S, Singh R, Malik S, et al. (2018): Prostate cancer health disparities: an immuno-biological perspective. Cancer Lett 414: 153-165.","DOI":"10.1016\/j.canlet.2017.11.011"},{"key":"ref-1655925","doi-asserted-by":"crossref","unstructured":"Gandhi J, Afridi A, Vatsia S, et al. (2018): The\u00a0molecular biology of\u00a0prostate cancer: current understanding and clinical implications. Prostate Cancer Prostatic Dis 21: 22-36.","DOI":"10.1038\/s41391-017-0023-8"},{"key":"ref-1655926","doi-asserted-by":"crossref","unstructured":"Matsushita M, Fujita K, Nonomura N (2020): Influence of\u00a0diet and nutrition on prostate cancer. Int J Mol Sci 21: 1447.","DOI":"10.3390\/ijms21041447"},{"key":"ref-1655927","doi-asserted-by":"crossref","unstructured":"Gillessen S, Attard G, Beer TM, et al. (2020): Management of\u00a0patients with advanced prostate cancer: report of\u00a0the\u00a0advanced prostate cancer consensus conference 2019. Eur Urol 77: 508-547.","DOI":"10.1016\/j.eururo.2020.01.012"},{"key":"ref-1655928","doi-asserted-by":"crossref","unstructured":"Choi E, Buie J, Camacho J, et al. (2022): Evolution of\u00a0androgen deprivation therapy (ADT) and its new emerging modalities in prostate cancer: an update for practicing urologists, clinicians and medical providers. Res Rep Urol 2022: 87-108.","DOI":"10.2147\/RRU.S303215"},{"key":"ref-1655929","doi-asserted-by":"crossref","unstructured":"Coppola U, Ristoratore F, Albalat R, D\u2019Aniello S (2019): The\u00a0evolutionary landscape of\u00a0the\u00a0Rab family in chordates. Cell Mol Life Sci 76: 4117-4130.","DOI":"10.1007\/s00018-019-03103-7"},{"key":"ref-1655930","doi-asserted-by":"crossref","unstructured":"Qin X, Wang J, Wang X, et al. (2017): Targeting Rabs as a\u00a0novel therapeutic strategy for cancer therapy. Drug discovery today. Drug Discov Today 22: 1139-1147.","DOI":"10.1016\/j.drudis.2017.03.012"},{"key":"ref-1655931","doi-asserted-by":"crossref","unstructured":"Duncan ED, Lencer E, Linklater E, Prekeris R (2021): Methods to study the\u00a0unique SOCS box domain of\u00a0the\u00a0Rab40 small GTPase subfamily. In: Rab GTPases: Methods and Protocols; 163-179.","DOI":"10.1007\/978-1-0716-1346-7_11"},{"key":"ref-1655932","doi-asserted-by":"crossref","unstructured":"Shahabi A, Naghili B, Ansarin K, Zarghami N (2019): The\u00a0relationship between microRNAs and Rab family GTPases in human cancers. J Cell Physiol 234: 12341-12352.","DOI":"10.1002\/jcp.28038"},{"key":"ref-1655933","doi-asserted-by":"crossref","unstructured":"Zhao Y, Xiong X, Sun Y (2020): Cullin-RING Ligase 5: Functional characterization and its role in human cancers. Semin Cancer Biol 67: 61-79.","DOI":"10.1016\/j.semcancer.2020.04.003"},{"key":"ref-1655934","doi-asserted-by":"crossref","unstructured":"Wu H, Dong X, Liao L, Huang L (2022): An integrative analysis identifying RAB40C as an oncogenic immune protein and prognostic marker of\u00a0lung squamous cell carcinoma. Pharmacogenom Pers Med 15: 525-537.","DOI":"10.2147\/PGPM.S357166"},{"key":"ref-1655935","doi-asserted-by":"crossref","unstructured":"Khakpour G, Noruzinia M, Izadi P, et al. (2017): Methylomics of\u00a0breast cancer: seeking epimarkers in peripheral blood of\u00a0young subjects. Tumour Biol 39: 1010428317695040.","DOI":"10.1177\/1010428317695040"},{"key":"ref-1655936","doi-asserted-by":"crossref","unstructured":"Wang X, Li Y, He M, et al. (2022): UbiBrowser 2.0: a\u00a0comprehensive resource for proteome-wide known and predicted ubiquitin ligase\/deubiquitinase\u2013substrate interactions in eukaryotic species. Nucleic Acids Res 50: D719-D728.","DOI":"10.1093\/nar\/gkab962"},{"key":"ref-1655937","doi-asserted-by":"crossref","unstructured":"Mbaeri T, Nwadi U, Abiahu J, et al. (2018): Correlation between prostate specific antigen, digital rectal examination and histology in patients with prostate cancer. Niger J Med 27: 212-218.","DOI":"10.4103\/1115-2613.278783"},{"key":"ref-1655938","doi-asserted-by":"crossref","unstructured":"Okpua NC, Okekpa SI, Njaka S, Emeh AN (2021): Clinical diagnosis of\u00a0prostate cancer using digital rectal examination and prostate-specific antigen tests: a\u00a0systematic review and meta-analysis of\u00a0sensitivity and specificity. Afr J Urol 27: 1-9.","DOI":"10.1186\/s12301-021-00129-x"},{"key":"ref-1655939","unstructured":"Kuppusamy S, Quek KF, Rajandram R, et al. (2018): Revisiting prostate specific antigen density (PSAD): a\u00a0prospective analysis in predicting the\u00a0histology of\u00a0prostate biopsy. Int J Clin Exp Med 11: 3873-3879."},{"key":"ref-1655940","doi-asserted-by":"crossref","unstructured":"Duffy MJ (2020): Biomarkers for prostate cancer: prostate-specific antigen and beyond. Clin Chem Lab Med 58: 326-339.","DOI":"10.1515\/cclm-2019-0693"},{"key":"ref-1655941","doi-asserted-by":"crossref","unstructured":"Garrido MM, Marta JC, Bernardino RM, et al. (2022): The\u00a0Percentage of\u00a0[\u20132] pro-prostate-specific antigen and the\u00a0prostate health index outperform prostate-specific antigen and the\u00a0percentage of\u00a0free prostate-specific antigen in the\u00a0detection of\u00a0clinically significant prostate cancer and can be used as reflex tests. Arch Pathol Lab Med 146: 691-700.","DOI":"10.5858\/arpa.2021-0079-OA"},{"key":"ref-1655942","doi-asserted-by":"crossref","unstructured":"Munteanu VC, Munteanu RA, Gulei D, et al. (2020): PSA based biomarkers, imagistic techniques and combined tests for a\u00a0better diagnostic of\u00a0localized prostate cancer. Diagnostics 10: 806.","DOI":"10.3390\/diagnostics10100806"},{"key":"ref-1655943","doi-asserted-by":"crossref","unstructured":"Shahryari A, Jazi MS, Mohammadi S, et al. (2019): Development and clinical translation of\u00a0approved gene therapy products for genetic disorders. Front Genet 10: 868.","DOI":"10.3389\/fgene.2019.00868"},{"key":"ref-1655944","doi-asserted-by":"crossref","unstructured":"Armstrong AJ, Lin P, Tombal B, et al. (2020): Five-year survival prediction and safety outcomes with enzalutamide in men with chemotherapy-na\u00efve metastatic castration-resistant prostate cancer from the\u00a0PREVAIL trial. Eur Urol 78: 347-357.","DOI":"10.1016\/j.eururo.2020.04.061"},{"key":"ref-1655945","doi-asserted-by":"crossref","unstructured":"Hassanipour S, Delam H, Arab-Zozani M, et al. (2020): Survival rate of\u00a0prostate cancer in Asian countries: a\u00a0systematic review and meta-analysis. Ann Glob Health 86: 1.","DOI":"10.5334\/aogh.2607"},{"key":"ref-1655946","doi-asserted-by":"crossref","unstructured":"Schroeder A, Herrmann A, Cherryholmes G, et al. (2014): Loss of\u00a0androgen receptor expression promotes a\u00a0stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer Res 74: 1227-1237.","DOI":"10.1158\/0008-5472.CAN-13-0594"},{"key":"ref-1655947","doi-asserted-by":"crossref","unstructured":"Qiao J, Kang J, Ishola TA, et al. (2008): Gastrin-releasing peptide receptor silencing suppresses the\u00a0tumorigenesis and metastatic potential of\u00a0neuroblastoma. Proc Natl Acad Sci USA 105: 12891-12896.","DOI":"10.1073\/pnas.0711861105"},{"key":"ref-1655948","doi-asserted-by":"crossref","unstructured":"Day JP, Whiteley E, Freeley M, et al. (2018): RAB40C regulates RACK1 stability via the\u00a0ubiquitin\u2013proteasome system. Future Sci OA 4: FSO317.","DOI":"10.4155\/fsoa-2018-0022"},{"key":"ref-1655949","doi-asserted-by":"crossref","unstructured":"Neumann AJ, Prekeris R (2023): A\u00a0Rab-bit hole: Rab40 GTPases as new regulators of\u00a0the\u00a0actin cytoskeleton and cell migration. Front Cell Dev Biol 11.","DOI":"10.3389\/fcell.2023.1268922"},{"key":"ref-1655950","doi-asserted-by":"crossref","unstructured":"Han KJ, Mikalayeva V, Gerber SA, et al. (2022): Rab40c regulates focal adhesions and PP6 activity by controlling ANKRD28 ubiquitylation. Life Sci Alliance 5: 9.","DOI":"10.26508\/lsa.202101346"},{"key":"ref-1655951","unstructured":"Linklater ES (2020): Regulation of\u00a0cancer cell migration and invasion by Rab40b. University of\u00a0Colorado Denver, Anschutz Medical Campus."},{"key":"ref-1655952","doi-asserted-by":"crossref","unstructured":"Weidle UH, Birzele F, Auslaender S, Brinkmann U\u00a0(2021): Down-regulated micrornas in gastric carcinoma may be targets for therapeutic intervention and replacement therapy. Anticancer Res 41: 4185-4202.","DOI":"10.21873\/anticanres.15223"},{"key":"ref-1655953","doi-asserted-by":"crossref","unstructured":"Garber JJ, Mallick EM, Scanlon KM, et al. (2018): Attaching-and-effacing pathogens exploit junction regulatory activities of\u00a0N-WASP and SNX9 to disrupt the\u00a0intestinal barrier. Cell Mol Gastroenterol Hepatol 5: 273-288.","DOI":"10.1016\/j.jcmgh.2017.11.015"},{"key":"ref-1655954","doi-asserted-by":"crossref","unstructured":"Blue RE, Curry EG, Engels NM, et al. (2018): How alternative splicing affects membrane-trafficking dynamics. J Cell Sci 131: jcs216465.","DOI":"10.1242\/jcs.216465"},{"key":"ref-1655955","doi-asserted-by":"crossref","unstructured":"Bendris N, Schmid SL (2017): Endocytosis, metastasis and beyond: Multiple facets of\u00a0SNX9. Trends Cell Biol 27: 189-200.","DOI":"10.1016\/j.tcb.2016.11.001"},{"key":"ref-1655956","doi-asserted-by":"crossref","unstructured":"Tanigawa K, Maekawa M, Kiyoi T, et al. (2019): SNX9 determines the\u00a0surface levels of\u00a0integrin \uf0621 in vascular endothelial cells: Implication in poor prognosis of\u00a0human colorectal cancers overexpressing SNX9. J Cell Physiol 234: 17280-17294.","DOI":"10.1002\/jcp.28346"},{"key":"ref-1655957","doi-asserted-by":"crossref","unstructured":"Trefny MP, Kirchhammer N, Auf der Maur P, et al. (2023): Deletion of\u00a0SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. Nat Commun 14: 86.","DOI":"10.1038\/s41467-022-35583-w"},{"key":"ref-1655958","doi-asserted-by":"crossref","unstructured":"Snigdha K, Gangwani KS, Lapalikar GV, et al. (2019): Hippo signaling in cancer: lessons from Drosophila models. Front Cell Dev Biol 7: 85.","DOI":"10.3389\/fcell.2019.00085"},{"key":"ref-1655959","doi-asserted-by":"crossref","unstructured":"Li FL, Guan KL (2022): The\u00a0two sides of\u00a0Hippo pathway in cancer. Semin Cancer Biol 85: 33-42.","DOI":"10.1016\/j.semcancer.2021.07.006"},{"key":"ref-1655960","doi-asserted-by":"crossref","unstructured":"Koinis F, Chantzara E, Samarinas M, et al. (2022): Emerging role of\u00a0YAP and the\u00a0Hippo pathway in prostate cancer. Biomedicines 10: 2834.","DOI":"10.3390\/biomedicines10112834"},{"key":"ref-1655961","doi-asserted-by":"crossref","unstructured":"Coffey K (2021): Targeting the\u00a0Hippo pathway in prostate cancer: what\u2019s new? Cancers 13: 611.","DOI":"10.3390\/cancers13040611"}],"container-title":["Central European Journal of Immunology"],"original-title":[],"link":[{"URL":"https:\/\/ceji.termedia.pl\/pdf-194106-135139","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ceji.termedia.pl\/pdf-194106-135139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:48:17Z","timestamp":1769158097000},"score":1,"resource":{"primary":{"URL":"https:\/\/ceji.termedia.pl\/RAB40C-regulates-SNX9-stability-via-the-ubiquitin-proteasome-system-and-modulates,194106,0,2.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":42,"alternative-id":["194106"],"URL":"https:\/\/doi.org\/10.5114\/ceji.2025.156367","relation":{},"ISSN":["1426-3912","1644-4124"],"issn-type":[{"value":"1426-3912","type":"print"},{"value":"1644-4124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}