{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:00:28Z","timestamp":1780981228876,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health","award":["L4\/28"],"award-info":[{"award-number":["L4\/28"]}]},{"name":"Ministry of Health","award":["L3\/25"],"award-info":[{"award-number":["L3\/25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mechanisms of primary and acquired resistance are responsible for treatment failure with the Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) in the majority of patients with advanced Non-Small-Cell Lung Cancer (NSCLC) carrying EGFR-activating mutations. MicroRNAs (miRNAs) are important modulators of EGFR signaling in lung cancer. Recent studies suggested the role of miR-23c as a tumor suppressor or oncogenic miRNA in different tumor types. However, the role of miR-23c in NSCLC carrying EGFR mutations and its involvement in resistance to EGFR-TKIs has not been explored yet. We found that miR-23c was strongly downregulated in H1975 and HCC827-Gefitinib-Resistant (GR) NSCLC cell lines with intrinsic and acquired resistance to gefitinib, respectively, as compared to gefitinib-sensitive cell lines. Moreover, we demonstrated that miR-23c mimic inhibited proliferation, migration, invasion, and epithelial\u2013mesenchymal transition of resistant cells and that Interleukin-6 Receptor (IL-6R) is a direct target of miR-23c in H1975 and HCC827-GR cell lines. Importantly, miR-23c mimic re-sensitized NSCLC-resistant cells to gefitinib, whereas the combination of miR-23c mimic with a neutralizing IL-6R antibody potentiated the sensitivity to the drug. Collectively, our data demonstrated that miR-23c acts as a tumor suppressor in NSCLC cell lines carrying EGFR mutations and that the axis miR-23c\/IL-6R might represent a potential target for the development of therapeutic approaches to overcome resistance to gefitinib.<\/jats:p>","DOI":"10.3390\/cells15121043","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T02:32:46Z","timestamp":1780885966000},"page":"1043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MiR-23c Regulates the Resistance to Gefitinib in EGFR Mutant Non-Small-Cell Lung Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7309-1719","authenticated-orcid":false,"given":"Brigitta","family":"Ignoto","sequence":"first","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5854-9924","authenticated-orcid":false,"given":"Ilaria Assunta","family":"Parisi","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8164-1704","authenticated-orcid":false,"given":"Cristin","family":"Roma","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6488-9740","authenticated-orcid":false,"given":"Rosa","family":"Camerlingo","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Dotolo","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Tufano","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-4110","authenticated-orcid":false,"given":"Monica Rosaria","family":"Maiello","sequence":"additional","affiliation":[{"name":"Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. 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