{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T06:55:58Z","timestamp":1769583358709,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T00:00:00Z","timestamp":1666137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Narayana Nethralaya Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Advanced retinoblastoma (Rb) tumors display high metastatic spread to distant tissues, causing a potent threat to vision and life. Through transcriptomic profiling, we discovered key upregulated genes that belonged to the epithelial\u2013mesenchymal transition (EMT) and chemotherapy resistance pathways in advanced Rb tumors. Through in vitro models, we further showed that Rb null tumor cells under prolonged chemo drug exposure, acquires a metastasis-like phenotype through the EMT program mediated by ZEB1 and SNAI2 and these cells further acquires chemotherapeutic resistance through cathepsin-L- and MDR1-mediated drug efflux mechanisms. Using a miRNA microarray, we identified miR-181a-5p as being significantly reduced in advanced Rb tumors, which was associated with an altered EMT and drug-resistance genes. We showed that enhancing miR-181a-5p levels in Rb null chemo-resistant sublines reduced the ZEB1 and SNAI2 levels and halted the mesenchymal transition switch, further reducing the drug resistance. We thus identified miR-181a-5p as a therapeutically exploitable target for EMT-triggered drug-resistant cancers that halted their invasion and migration and sensitized them to low-dose chemotherapy drugs.<\/jats:p>","DOI":"10.3390\/cancers14205124","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T20:32:23Z","timestamp":1666211543000},"page":"5124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8104-8652","authenticated-orcid":false,"given":"Vishnu","family":"Suresh Babu","sequence":"first","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India"},{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anadi","family":"Bisht","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwin","family":"Mallipatna","sequence":"additional","affiliation":[{"name":"Retinoblastoma Service, Narayana Nethralaya, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"SA","sequence":"additional","affiliation":[{"name":"Agilent Technologies India Pvt. Ltd., Bangalore 560048, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gagan","family":"Dudeja","sequence":"additional","affiliation":[{"name":"Retinoblastoma Service, Narayana Nethralaya, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramaraj","family":"Kannan","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Shetty","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-3107","authenticated-orcid":false,"given":"Nilanjan","family":"Guha","sequence":"additional","affiliation":[{"name":"Agilent Technologies India Pvt. Ltd., Bangalore 560048, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, Herestraat 49, bus 911, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-5891","authenticated-orcid":false,"given":"Arkasubhra","family":"Ghosh","sequence":"additional","affiliation":[{"name":"GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore 560099, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gupta, H., Malaichamy, S., Mallipatna, A., Murugan, S., Jeyabalan, N., Suresh Babu, V., Ghosh, A., Ghosh, A., Santhosh, S., and Seshagiri, S. 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