{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:46:45Z","timestamp":1791866805164,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American University of Beirut - University Research Board","award":["27611"],"award-info":[{"award-number":["27611"]}],"id":[{"id":"https:\/\/ror.org\/04pznsd21","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American University of Beirut - University Research Board","award":["26748"],"award-info":[{"award-number":["26748"]}],"id":[{"id":"https:\/\/ror.org\/04pznsd21","id-type":"ROR","asserted-by":"crossref"}]},{"award":["27611"],"award-info":[{"award-number":["27611"]}],"id":[{"id":"https:\/\/ror.org\/04pznsd21","id-type":"ROR","asserted-by":"publisher"}]},{"award":["26748"],"award-info":[{"award-number":["26748"]}],"id":[{"id":"https:\/\/ror.org\/04pznsd21","id-type":"ROR","asserted-by":"publisher"}]},{"name":"French Embassy in Lebanon - Safar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>CircRNAs are key regulators of gene expression. The functional roles of exonic versus exon\u2013intron circRNAs in early breast cancer remain unclear. Connexin-43 (GJA1) generates exonic circRNA (ecircRNA) hsa_circ_0077755 (circ_755) and exon\u2013intron circRNA (EIcircRNA), hsa_circ_0077753 (circ_753), both linked to increased breast cancer risk. We examined their structural, molecular, and phenotypic roles in transient and stable knockdown S1 breast epithelial cells, using RT-qPCR, dual-luciferase, lumen formation and invasion assays, and extracellular vesicle (EV) analysis. Knockdown of cytoplasm-enriched circ_755 reduced Connexin-43 transcript and protein, whereas knockdown of nuclear-enriched circ_753 preserved GJA1. Both induced lumen disruption, \u03b2-catenin disorganization, increased invasion, and regulated onco-miR-182. More pronounced miR-182 upregulation and broader repression of tumor-suppressive targets (BCL2, FOXO1, RECK) were observed in circ_753 knockdown cells, alongside concurrent depletion of hsa_circ_0008932 (circ_8932), which is predicted to interact with miR-182. Similar reciprocal changes in circRNA\/miR-182 were observed in released EVs. These data highlight circRNA-miR-182 networks with distinct effects on tumor initiation and potential value as breast cancer biomarkers.<\/jats:p>","DOI":"10.3390\/ijms27198849","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:31:31Z","timestamp":1791203491000},"page":"8849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of GJA1-Derived circ_753 and circ_755 Differentially Modulates miR-182-5p Expression and Breast Cancer-Associated Phenotypes"],"prefix":"10.3390","volume":"27","author":[{"given":"Nour","family":"Maatouk","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9phine","family":"Briand","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, 49055 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Ismael","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1763-712X","authenticated-orcid":false,"given":"Serena","family":"Andraos","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8321-4025","authenticated-orcid":false,"given":"Abdallah","family":"Kurdi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Leli\u00e8vre","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, 49055 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-4999","authenticated-orcid":false,"given":"Rihab","family":"Nasr","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-1736","authenticated-orcid":false,"given":"Rabih","family":"Talhouk","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,3]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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