{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:43:57Z","timestamp":1790855037904,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T00:00:00Z","timestamp":1651190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Radiotherapy resistance is an important cause of treatment failure in esophageal squamous cell carcinoma (ESCC). Circular RNAs have attracted a lot of attention in cancer research, but their role in ESCC radiosensitivity has not been elucidated yet. Here, we aimed to evaluated the functional impacts of circ-0007022 on ESCC radiosensitivity. In this study, a stable radiotherapy-resistant cell line was established and verified by a series of functional experiments. Subsequently, high-throughput sequencing revealed that circ-0007022 was significantly overexpressed in the radiotherapy-resistant cell line and this conclusion was verified in ESCC patients\u2019 tumor tissues by real-time quantitative PCR. Moreover, loss-of-function and overexpression experiments <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> revealed that, after irradiation, the abilities of proliferation and migration in circ-0007022-overexpressing stable transgenic strain were significantly higher than that in circ-0007022-knockdown stable transgenic strain. Additionally, RNA Immunoprecipitation, RNA pull-down, luciferase reporter assays, and fluorescence <jats:italic>in situ<\/jats:italic> hybridization experiments demonstrated the mechanism of how circ-0007022 could sponge miR-338-3p and upregulate downstream target of miR-338-3p, neuropilin-1 (NRP1). Moreover, NRP1 led to poor prognosis for ESCC patients receiving radiotherapy, and NRP1 knock-down enhanced radiosensitivity of ESCC cells. Furthermore, circ-0007022 overexpression activated Epithelial-to-mesenchymal transition and PI3K\/Akt pathway, and NRP1 knock-down could reversed this phenomenon. Finally, Akt Inhibitor reversed circ-0007022s role in radiotherapy in ESCC cells. Taken together, the circ-0007022\/miR-338-3p\/NRP1 axis enhances the radiation resistance of ESCC cells <jats:italic>via<\/jats:italic> regulating EMT and PI3K\/Akt pathway. The new circRNA circ-0007022 is thus expected to be a therapeutic target for ESCC patients.<\/jats:p>","DOI":"10.3389\/fgene.2022.854097","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T07:38:31Z","timestamp":1651217911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A Circ-0007022\/miR-338-3p\/Neuropilin-1 Axis Reduces the Radiosensitivity of Esophageal Squamous Cell Carcinoma by Activating Epithelial-To-Mesenchymal Transition and PI3K\/AKT Pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Junpeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshuang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/s41388-020-01530-6","article-title":"Epigenetic Targeting of Neuropilin-1 Prevents Bypass Signaling in Drug-Resistant Breast Cancer","volume":"40","author":"Abdullah","year":"2021","journal-title":"Oncogene"},{"key":"B2","doi-asserted-by":"publisher","first-page":"855","DOI":"10.6004\/jnccn.2019.0033","article-title":"Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology","volume":"17","author":"Ajani","year":"2019","journal-title":"J. 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