{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:12Z","timestamp":1785424992458,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Proyecto Iniciaci\u00f3n en Investigaci\u00f3n Asociativa","award":["IUP23-13"],"award-info":[{"award-number":["IUP23-13"]}]},{"name":"Universidad del Desarrollo Vicerrector\u00eda de Investigaci\u00f3n y Doctorados","award":["CI202503"],"award-info":[{"award-number":["CI202503"]}]},{"award":["CI202503"],"award-info":[{"award-number":["CI202503"]}],"id":[{"id":"https:\/\/ror.org\/05y33vv83","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"ANID Fondecyt Iniciaci\u00f3n","doi-asserted-by":"publisher","award":["11260424"],"award-info":[{"award-number":["11260424"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondecyt","doi-asserted-by":"publisher","award":["1240485"],"award-info":[{"award-number":["1240485"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Long non-coding RNAs (lncRNAs) are regulatory transcripts that contribute to diverse cellular processes and are increasingly recognized for their involvement in human diseases including cancer. In this context, long intergenic non-protein-coding RNA 1770 (LINC01770), also known as RRFERV, has been involved in nasopharyngeal cancer progression. However, its role in breast cancer (BC) remains unexplored. Here, we propose that LINC01770 plays a pivotal role in the development of aggressiveness traits such as invasion, migration, stemness, and tumorigenesis in BC cells. Methods: The LINC01770 overexpression was performed in BC cells using lentiviral transduction. Stemness and epithelial\u2013mesenchymal transition markers, CD133+\/44+ populations, cell migration, cell invasion, tumorigenesis in vitro, and chemoresistance were subsequently assessed via quantitative reverse transcription polymerase chain reaction (RT-qPCR), flow cytometry, Boyden chambers, soft agar, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. LINC01770 expression in BC tissues and mechanistic analyses were performed in silico. Results: LINC01770 promotes cell migration and invasion accompanied by increased expression of EMT-associated genes. Moreover, elevated LINC01770 levels lead to an expansion of CD133+\/CD44+ cell populations and upregulation of stemness-related genes as well as increase tumorigenic capacity in vitro. In contrast, no significant effects on drug resistance were observed. Finally, bioinformatic analyses suggest a putative LINC01770\/miR-335-5p\/OCT4 regulatory axis, consistent with the observed increase in OCT4 expression after LINC01770 overexpression. Conclusions: Our findings demonstrate that LINC01770 drives BC progression by promoting migration, invasion, and stemness features via the miR-335-5p\/OCT4 axis. To our knowledge, this is the first study identifying LINC01770 as a potential therapeutic target in BC.<\/jats:p>","DOI":"10.3390\/ph19071039","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:39:11Z","timestamp":1783078751000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LINC01770 Is Associated with Stem-like Features and Aggressive Traits in Breast Cancer Cells Through a Putative miR-335-5p\/OCT4 Axis"],"prefix":"10.3390","volume":"19","author":[{"given":"Javier","family":"Gasson","sequence":"first","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7780272, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"B\u00f6hmwald","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7780272, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1612-171X","authenticated-orcid":false,"given":"Juan P.","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica, Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad de Tarapac\u00e1, Arica 1000007, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-6686","authenticated-orcid":false,"given":"Mauricio A.","family":"Retamal","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7780272, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-3089","authenticated-orcid":false,"given":"Pablo","family":"P\u00e9rez-Moreno","sequence":"additional","affiliation":[{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Instituto de Ciencias e Innovaci\u00f3n en Medicina (ICIM), Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7780272, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"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. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40164-022-00363-1","article-title":"Breast cancer heterogeneity and its implication in personalized precision therapy","volume":"12","author":"Guo","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41392-024-02108-4","article-title":"Breast cancer: Pathogenesis and treatments","volume":"10","author":"Xiong","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.cell.2019.10.017","article-title":"The Role of Non-coding RNAs in Oncology","volume":"179","author":"Slack","year":"2019","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.gpb.2015.09.006","article-title":"Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer","volume":"14","author":"Fang","year":"2016","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s40001-025-02420-x","article-title":"LncRNA-MALAT1 promotes triple-negative breast cancer progression and function as ceRNA to target REEP5 by sponging miR-106a-5p","volume":"30","author":"Yang","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1038\/s41598-024-52953-0","article-title":"Long noncoding RNA SNHG1 promotes breast cancer progression by regulating the miR-641\/RRS1 axis","volume":"14","author":"Deng","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ncrna.2016.09.002","article-title":"Integrated analysis of dysregulated lncRNA expression in breast cancer cell identified by RNA-seq study","volume":"1","author":"Tripathi","year":"2016","journal-title":"Noncoding RNA Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/JS9.0000000000002099","article-title":"RRFERV stabilizes TEAD1 expression to mediate nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis","volume":"111","author":"Xu","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1111\/febs.16046","article-title":"The gate to metastasis: Key players in cancer cell intravasation","volume":"289","author":"Sznurkowska","year":"2022","journal-title":"FEBS J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sadri, M., Shafaghat, Z., Roozbehani, M., Dorfaki, M., Kheiri, F., Heidari, S., Mahmoudi, A., and Faraji, F. (2026). Targeting cancer stem cells as the most aggressive and tumor-initiating cells. Transl. Oncol., 65.","DOI":"10.1016\/j.tranon.2026.102669"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/jclinpath-2017-204739","article-title":"Cancer stem cells in colorectal cancer: A review","volume":"71","author":"Munro","year":"2018","journal-title":"J. Clin. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13148-017-0413-8","article-title":"MicroRNA-335-5p is a potential suppressor of metastasis and invasion in gastric cancer","volume":"9","author":"Polakovicova","year":"2017","journal-title":"Clin. Epigenet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.2147\/OTT.S305098","article-title":"Functions and Targets of miR-335 in Cancer","volume":"14","author":"Ye","year":"2021","journal-title":"OncoTargets Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Weidenfeld, K., and Barkan, D. (2018). EMT and Stemness in Tumor Dormancy and Outgrowth: Are They Intertwined Processes?. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00381"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Walcher, L., Kistenmacher, A.K., Suo, H., Kitte, R., Dluczek, S., Strau\u00df, A., Blaudszun, A.R., Yevsa, T., Fricke, S., and Kossatz-Boehlert, U. (2020). Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01280"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ordaz-Ramos, A., Tellez-Jimenez, O., and Vazquez-Santillan, K. (2023). Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1221175"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.3892\/mmr.2020.11196","article-title":"lncRNA MALAT1 modulates cancer stem cell properties of liver cancer cells by regulating YAP1 expression via miR-375 sponging","volume":"22","author":"Zhao","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102630","DOI":"10.1016\/j.jbc.2022.102630","article-title":"Long noncoding RNA HOTAIR regulates the stemness of breast cancer cells via activation of the NF-\u03baB signaling pathway","volume":"298","author":"Wang","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25161","DOI":"10.18632\/oncotarget.4629","article-title":"Coupling the modules of EMT and stemness: A tunable \u2018stemness window\u2019 model","volume":"6","author":"Jolly","year":"2015","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12943-016-0579-2","article-title":"EMT and stemness: Flexible processes tuned by alternative splicing in development and cancer progression","volume":"16","author":"Pradella","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/1878-0261.12096","article-title":"Revisiting epithelial-mesenchymal transition in cancer metastasis: The connection between epithelial plasticity and stemness","volume":"11","author":"Liao","year":"2017","journal-title":"Mol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9136","DOI":"10.1002\/jcp.26847","article-title":"Epithelial-to-mesenchymal transition and cancer stem cells contribute to breast cancer heterogeneity","volume":"233","author":"Hong","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1158\/0008-5472.CAN-20-2801","article-title":"YAP and \u03b2-Catenin Cooperate to Drive Oncogenesis in Basal Breast Cancer","volume":"81","author":"Quinn","year":"2021","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cell.2015.07.013","article-title":"Alternative Wnt Signaling Activates YAP\/TAZ","volume":"162","author":"Park","year":"2015","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12943-020-01276-5","article-title":"Wnt signaling in breast cancer: Biological mechanisms, challenges and opportunities","volume":"19","author":"Xu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41392-024-01848-7","article-title":"Tumor initiation and early tumorigenesis: Molecular mechanisms and interventional targets","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.2147\/OTT.S191740","article-title":"lncRNA SLCO4A1-AS1 promotes growth and invasion of bladder cancer through sponging miR-335-5p to upregulate OCT4","volume":"12","author":"Yang","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_29","first-page":"1853","article-title":"MiR-335-5p inhibits proliferation of Huh-7 liver cancer cells via targeting the Oct4\/Akt pathway","volume":"25","author":"Ji","year":"2021","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12935-017-0398-6","article-title":"miR-335 negatively regulates osteosarcoma stem cell-like properties by targeting POU5F1","volume":"17","author":"Guo","year":"2017","journal-title":"Cancer Cell Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104738","DOI":"10.1016\/j.yexmp.2021.104738","article-title":"Tumour suppressor role of microRNA-335-5p in esophageal squamous cell carcinoma by targeting TTK (Mps1)","volume":"124","author":"Suyal","year":"2022","journal-title":"Exp. Mol. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"165432","DOI":"10.1016\/j.bbadis.2019.03.005","article-title":"Role of OCT4 in cancer stem-like cells and chemotherapy resistance","volume":"1866","author":"Mohiuddin","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"312","DOI":"10.15283\/ijsc20097","article-title":"The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review","volume":"13","author":"Zhang","year":"2020","journal-title":"Int. J. Stem Cells"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Moreno, P., Riquelme, I., Bizama, C., Vergara-G\u00f3mez, L., Tapia, J.C., Brebi, P., Garc\u00eda, P., and Roa, J.C. (2024). LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126740"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gks596","article-title":"Primer3\u2014New capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/BF00300234","article-title":"Determination of subcutaneous tumor size in athymic (nude) mice","volume":"24","author":"Tomayko","year":"1989","journal-title":"Cancer Chemother. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:06:58Z","timestamp":1783080418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":36,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ph19071039"],"URL":"https:\/\/doi.org\/10.3390\/ph19071039","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}