Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis
Abstract Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01593-w |
| _version_ | 1797453911075848192 |
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| author | Dong Li Wujie Wang Bin Liu Die Jin Yang Wang Guanghui He Lei Guo Wen Liu Yuliang Li |
| author_facet | Dong Li Wujie Wang Bin Liu Die Jin Yang Wang Guanghui He Lei Guo Wen Liu Yuliang Li |
| author_sort | Dong Li |
| collection | DOAJ |
| description | Abstract Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed after I-125 treatment in HCC cell lines and tissues and is a key regulator of I-125-induced anticancer effects. CircSEC11A acts as a competing endogenous RNA (ceRNA) to sponge miR-3529-3p, promoting the expression of zinc fingers and homeoboxes 2 (ZHX2) and enhancing I-125-induced anticancer effects. Dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and fluorescence in situ hybridization were thereafter performed to verify the interaction among the molecules. Anticancer effects were detected using CCK-8, flow cytometry, TUNEL, EdU, transwell, and wound healing assays. Furthermore, ZHX2 transcriptionally inhibits GADD34, a negative regulator of endoplasmic reticulum stress (ERS), to enhance I-125- induced anticancer effects in vivo and in vitro. In conclusion, we characterized circSEC11A as a novel regulator of I-125-induced anticancer effects in HCC via miR-3529-3p/ZHX2/GADD34 axis-mediated ERS. Thus, circSEC11A may act as a potential therapeutic target for I-125 implantation in the clinic. |
| first_indexed | 2024-03-09T15:29:41Z |
| format | Article |
| id | doaj.art-dcb34ff126604f538c8389c90c0ed29a |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-09T15:29:41Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-dcb34ff126604f538c8389c90c0ed29a2023-11-26T12:21:33ZengNature Publishing GroupCell Death Discovery2058-77162023-08-019111610.1038/s41420-023-01593-wCharacterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axisDong Li0Wujie Wang1Bin Liu2Die Jin3Yang Wang4Guanghui He5Lei Guo6Wen Liu7Yuliang Li8Department of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, Weifang Second People’s HospitalDepartment of Vascular Anomalies and Interventional Radiology, Children’s Hospital Affiliated to Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityDepartment of Interventional Medicine, The Second Hospital of Shandong UniversityAbstract Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed after I-125 treatment in HCC cell lines and tissues and is a key regulator of I-125-induced anticancer effects. CircSEC11A acts as a competing endogenous RNA (ceRNA) to sponge miR-3529-3p, promoting the expression of zinc fingers and homeoboxes 2 (ZHX2) and enhancing I-125-induced anticancer effects. Dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and fluorescence in situ hybridization were thereafter performed to verify the interaction among the molecules. Anticancer effects were detected using CCK-8, flow cytometry, TUNEL, EdU, transwell, and wound healing assays. Furthermore, ZHX2 transcriptionally inhibits GADD34, a negative regulator of endoplasmic reticulum stress (ERS), to enhance I-125- induced anticancer effects in vivo and in vitro. In conclusion, we characterized circSEC11A as a novel regulator of I-125-induced anticancer effects in HCC via miR-3529-3p/ZHX2/GADD34 axis-mediated ERS. Thus, circSEC11A may act as a potential therapeutic target for I-125 implantation in the clinic.https://doi.org/10.1038/s41420-023-01593-w |
| spellingShingle | Dong Li Wujie Wang Bin Liu Die Jin Yang Wang Guanghui He Lei Guo Wen Liu Yuliang Li Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis Cell Death Discovery |
| title | Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis |
| title_full | Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis |
| title_fullStr | Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis |
| title_full_unstemmed | Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis |
| title_short | Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis |
| title_sort | characterization of circsec11a as a novel regulator of iodine 125 radioactive seed induced anticancer effects in hepatocellular carcinoma via targeting zhx2 gadd34 axis |
| url | https://doi.org/10.1038/s41420-023-01593-w |
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