{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:08:45Z","timestamp":1773817725365,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Otago Innovation Limited"},{"DOI":"10.13039\/501100009193","name":"Royal Society of New Zealand Marsden Fund","doi-asserted-by":"crossref","award":["19-UOO-106"],"award-info":[{"award-number":["19-UOO-106"]}],"id":[{"id":"10.13039\/501100009193","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Otago Master\u2019s writing bursary"},{"name":"University of Otago Masters scholarship"},{"name":"PhD scholarship from the Cancer Research Trust of New Zealand"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer deaths, with resistance to targeted therapies posing a major clinical challenge. Drug-tolerant persister (DTP) cells are key contributors to resistance, and targeting them offers new strategies to enhance existing treatments. MicroRNAs (miRNAs), particularly the tumour-suppressive miR-15\/107 family, offer promise due to their ability to target multiple oncogenic pathways. This study evaluated a synthetic consensus miRNA mimic, conmiR-15\/107, in NSCLC cell line models. Dose\u2013response assays showed robust, dose-dependent growth inhibition in both EGFR-mutant (PC9) and KRAS-mutant (H358 and A549) lung adenocarcinoma cells, but not in the human bronchial epithelial cell line BEAS-2B. When combined with EGFR inhibitors (osimertinib and gefitinib) in PC9 cells, the mimics showed a higher rate of growth inhibition compared with the controls and reduced IC50 values. Similarly, conmiR-15\/107 enhanced growth inhibition by the KRAS inhibitors sotorasib and adagrasib in H358 cells. RT-qPCR confirmed downregulation of conmiR-15\/107 targets, including MEK1, BCL2 and BRCA1, suggesting a multi-target mechanism of action. Long-term assays showed that the mimics reduced the survival and delayed the proliferation of DTPs in osimertinib-treated PC9 cells as well as sotorasib-treated H358 cells. These findings support conmiR-15\/107 as a potential adjunct to targeted therapy, capable of enhancing treatment efficacy and delaying resistance in lung adenocarcinoma.<\/jats:p>","DOI":"10.3390\/ijms27062701","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T14:30:32Z","timestamp":1773671432000},"page":"2701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA Mimics Based on the miR-15\/107 Consensus Sequence Sensitise NSCLC Cells to Targeted Therapy"],"prefix":"10.3390","volume":"27","author":[{"given":"Carien","family":"Carpenter","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J. H.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-9688","authenticated-orcid":false,"given":"Nico van","family":"Zandwijk","sequence":"additional","affiliation":[{"name":"Sydney Local Health District, Sydney, NSW 2065, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine J.","family":"Drummond","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-5223","authenticated-orcid":false,"given":"Glen","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Dunedin 9054, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"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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