{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:48:35Z","timestamp":1785836915389,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203079"],"award-info":[{"award-number":["82203079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473069"],"award-info":[{"award-number":["82473069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82203079"],"award-info":[{"award-number":["82203079"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82473069"],"award-info":[{"award-number":["82473069"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fourth Hospital of Hebei Medical University","award":["2023C11"],"award-info":[{"award-number":["2023C11"]}]},{"award":["2023C11"],"award-info":[{"award-number":["2023C11"]}],"id":[{"id":"https:\/\/ror.org\/01mdjbm03","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hengrui Innovative Development Medical Cooperation Program of Hebei","award":["HR202502034"],"award-info":[{"award-number":["HR202502034"]}]},{"name":"Key Program of Hebei Natural Science Foundation","award":["H2024206222"],"award-info":[{"award-number":["H2024206222"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis, highlighting the urgent need to elucidate its molecular mechanisms to develop targeted therapies. Long non-coding RNAs (lncRNAs) play a critical role in cancer progression. However, the majority of lncRNAs involved in ESCC progression remain to be elucidated. Methods: We integrated bioinformatic analyses of the TCGA and GEO datasets to identify differentially expressed lncRNAs in ESCC, and the biological functions of the candidate lncRNA LINC01446 were investigated using loss-of-function assays in ESCC cell lines, including colony formation, wound healing, Transwell invasion, C11-BODIPY staining, malondialdehyde (MDA) quantification, and glutathione (GSH) evaluation. A nude mouse xenograft model was established for in vivo validation, and the underlying molecular mechanism was explored through RNA sequencing, fluorescence in situ hybridization (FISH), dual-luciferase reporter assays, AGO2-RIP, and rescue experiments. Results: LINC01446 was significantly upregulated in ESCC tissues and cell lines. Based on univariate analysis, high expression of LINC01446 was associated with poorer overall survival (OS). Functional studies showed that LINC01446 knockdown suppressed ESCC cell proliferation, migration, and invasion, promoted ferroptosis-related changes in vitro and was associated with increased lipid peroxidation and possible ferroptosis-related changes in vivo. Mechanistic analyses supported a regulatory relationship in which LINC01446 may function as a competing endogenous RNA (ceRNA) for miR-338-3p, thereby contributing to the upregulation of its downstream target, apurinic\/apyrimidinic endodeoxyribonuclease 1 (APEX1), in ESCC cells. Moreover, APEX1 was found to be overexpressed in ESCC and associated with poor OS. Conclusions: This study suggests that the LINC01446\/miR-338-3p\/APEX1 regulatory axis may contribute to ESCC progression and ferroptosis-related regulation. Additionally, LINC01446 and APEX1 represent promising prognostic biomarkers and therapeutic targets for ESCC.<\/jats:p>","DOI":"10.3390\/cancers18152496","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:15:22Z","timestamp":1785834922000},"page":"2496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LINC01446\/miR-338-3p\/APEX1 Axis Promotes Ferroptosis Defense and Progression in Esophageal Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"given":"Yunlong","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuman","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Tumor Radiotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-4624","authenticated-orcid":false,"given":"Lihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunotherapy, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050035, China"},{"name":"Cancer Research Institute of Hebei Province, Shijiazhuang 050011, China"},{"name":"China International Cooperation Laboratory of Stem Cell Research, Hebei Medical University, Shijiazhuang 050011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/cac2.12645","article-title":"Current status and perspectives of esophageal cancer: A comprehensive review","volume":"45","author":"Jiang","year":"2025","journal-title":"Cancer Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1016\/S0140-6736(24)02226-8","article-title":"Oesophageal cancer","volume":"404","author":"Yang","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41576-024-00693-2","article-title":"Targeting and engineering long non-coding RNAs for cancer therapy","volume":"25","author":"Coan","year":"2024","journal-title":"Nat. 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Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:39:16Z","timestamp":1785836356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":55,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152496"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152496","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}