{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:18:41Z","timestamp":1772507921444,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hellenic Foundation for Research and Innovation (H.F.R.I.)","award":["6318"],"award-info":[{"award-number":["6318"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>DROSHA protein is widely known for its essential role in the microRNA (miRNA\/miR) biogenesis pathway where, together with its co-factor DGCR8, it forms the \u201cMicroprocessor\u201d complex and catalyzes the primary miRNA (pri-miRNA) processing in the nucleus. Nevertheless, DROSHA also seems to participate in several miRNA-independent cellular mechanisms, such as transcriptional regulation, RNA processing and genome integrity maintenance. Hence, the present study aims to further investigate novel miRNA-independent activities of DROSHA protein, with potentially regulatory roles in the oncogenesis of human cancer cells. Our results reveal a new, strong profile of microprocessor-independent DROSHA localization at the Golgi apparatus in several human cancer cell lines of different tissue origin, with hepatic carcinoma, thyroid cancer, urothelial bladder cancer, colon carcinoma and melanoma being the cellular model systems herein examined. Notably, oncogenic activity, malignancy grade and metastatic capacity are shown to be strongly associated with DROSHA\u2019s compartmentalization at Golgi, a phenotype that does not seem to rely on p53 protein\u2019s functionality. Taken together, through employment of advanced confocal laser scanning microscopy (CLSM) and molecular modeling, we herein unveil the ability of DROSHA, but not AGO2 and DICER, to reside at Golgi, where DROSHA can physically interact with the GM130 Golgi-specific component, thus indicating DROSHA\u2019s engagement in non-canonical and miRNA-independent\u2014but also Golgi apparatus-dependent\u2014novel mechanisms that can be tightly coupled with malignancy dynamics and beneficially utilized as potential biomarkers and therapeutic targets for human cancer.<\/jats:p>","DOI":"10.3390\/ijms26199319","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:39:42Z","timestamp":1758710382000},"page":"9319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-Canonical Compartmentalization of DROSHA Protein at the Golgi Apparatus: miRNA Biogenesis-Independent Functionality in Human Cancer Cells of Diverse Tissue Origin"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9118-5382","authenticated-orcid":false,"given":"Eleni I.","family":"Theotoki","sequence":"first","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"},{"name":"Center of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 115 27 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panos","family":"Kakoulidis","sequence":"additional","affiliation":[{"name":"Department of Informatics and Telecommunications, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-745X","authenticated-orcid":false,"given":"Kostas A.","family":"Papavassiliou","sequence":"additional","affiliation":[{"name":"First University Department of Respiratory Medicine, \u201cSotiria\u201d Chest Hospital, Medical School, National and Kapodistrian University of Athens (NKUA), 115 27 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6694-6558","authenticated-orcid":false,"given":"Konstantinos-Stylianos","family":"Nikolakopoulos","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0919-0165","authenticated-orcid":false,"given":"Eleni N.","family":"Vlachou","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efthimia K.","family":"Basdra","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens (NKUA), 115 27 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-4527","authenticated-orcid":false,"given":"Athanasios G.","family":"Papavassiliou","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens (NKUA), 115 27 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6954-0740","authenticated-orcid":false,"given":"Ourania E.","family":"Tsitsilonis","sequence":"additional","affiliation":[{"name":"Section of Animal and Human Physiology, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerassimos E.","family":"Voutsinas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research (NCSR) \u201cDemokritos\u201d, 153 10 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-395X","authenticated-orcid":false,"given":"Athanassios D.","family":"Velentzas","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3419-2031","authenticated-orcid":false,"given":"Ema","family":"Anastasiadou","sequence":"additional","affiliation":[{"name":"Center of Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 115 27 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9535-2134","authenticated-orcid":false,"given":"Dimitrios J.","family":"Stravopodis","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 157 01 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lett, K.E., Logan, M.K., McLaurin, D.M., and Hebert, M.D. (2021). 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