{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:19Z","timestamp":1791563179602,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"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":["12275003"],"award-info":[{"award-number":["12275003"]}],"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":["NPT2020KFY19"],"award-info":[{"award-number":["NPT2020KFY19"]}],"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":["1608085QH216"],"award-info":[{"award-number":["1608085QH216"]}],"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":["KJ2021A0210"],"award-info":[{"award-number":["KJ2021A0210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014955","name":"State Key Laboratory of Nuclear Physics and Technology, Peking University","doi-asserted-by":"publisher","award":["12275003"],"award-info":[{"award-number":["12275003"]}],"id":[{"id":"10.13039\/501100014955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014955","name":"State Key Laboratory of Nuclear Physics and Technology, Peking University","doi-asserted-by":"publisher","award":["NPT2020KFY19"],"award-info":[{"award-number":["NPT2020KFY19"]}],"id":[{"id":"10.13039\/501100014955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014955","name":"State Key Laboratory of Nuclear Physics and Technology, Peking University","doi-asserted-by":"publisher","award":["1608085QH216"],"award-info":[{"award-number":["1608085QH216"]}],"id":[{"id":"10.13039\/501100014955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014955","name":"State Key Laboratory of Nuclear Physics and Technology, Peking University","doi-asserted-by":"publisher","award":["KJ2021A0210"],"award-info":[{"award-number":["KJ2021A0210"]}],"id":[{"id":"10.13039\/501100014955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["12275003"],"award-info":[{"award-number":["12275003"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["NPT2020KFY19"],"award-info":[{"award-number":["NPT2020KFY19"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["1608085QH216"],"award-info":[{"award-number":["1608085QH216"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["KJ2021A0210"],"award-info":[{"award-number":["KJ2021A0210"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Provincial Natural Science Research Project of Anhui Colleges","award":["12275003"],"award-info":[{"award-number":["12275003"]}]},{"name":"Provincial Natural Science Research Project of Anhui Colleges","award":["NPT2020KFY19"],"award-info":[{"award-number":["NPT2020KFY19"]}]},{"name":"Provincial Natural Science Research Project of Anhui Colleges","award":["1608085QH216"],"award-info":[{"award-number":["1608085QH216"]}]},{"name":"Provincial Natural Science Research Project of Anhui Colleges","award":["KJ2021A0210"],"award-info":[{"award-number":["KJ2021A0210"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Connexin 26 (Cx26) is a protein that constitutes a gap junction and is widely expressed in the liver. Abnormal expression of Cx26 is one of the important mechanisms of liver cancer, and is closely related to the transmission of radiation damage signals between cells. In the present study, we investigated the radiosensitivity of hepatocellular carcinoma (HCC) cells HepG2, with low expression of Cx26, and SK-hep-1, with high expression of Cx26 after X-ray irradiation. The cell survival, micronucleus formation and protein expressions of the mitogen-activated protein kinases (MAPK) signaling pathway were detected. The expression level of Cx26 could affect the radiosensitivity of liver cancer cells by affecting the phosphorylation of p38 and ERK proteins and regulating the expression of downstream NF-\u03baB. Cell lines with knock-out and overexpression of Cx26 were also built to confirm the findings. Our results suggested that Cx26 might play an important role in the radiosensitivity of liver cancer and could be a potential target for clinical radiotherapy of liver cancer.<\/jats:p>","DOI":"10.3390\/ijms232314644","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T03:58:16Z","timestamp":1669262296000},"page":"14644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Expression of Connexin 26 Regulates the Radiosensitivity of Hepatocellular Carcinoma Cells through a Mitogen-Activated Protein Kinases Signal Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Yuan","family":"Li","sequence":"first","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Tao","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Shang","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"},{"name":"Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqiong","family":"Sun","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichao","family":"Peng","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"},{"name":"Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1384-6024","authenticated-orcid":false,"given":"Ye","family":"Zhao","sequence":"additional","affiliation":[{"name":"Teaching & Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nrgastro.2010.100","article-title":"Hepatocellular carcinoma: A global view","volume":"7","author":"Yang","year":"2010","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: Trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.canlet.2017.10.008","article-title":"Precision diagnosis and treatment of liver cancer in China","volume":"412","author":"Fu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.5582\/bst.2021.01083","article-title":"Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China","volume":"15","author":"Liu","year":"2021","journal-title":"Biosci. Trends"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3349\/ymj.2009.50.5.601","article-title":"Challenge and Hope in Radiotherapy of Hepatocellular Carcinoma","volume":"50","author":"Seong","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.radonc.2014.02.001","article-title":"Is there a role for proton therapy in the treatment of hepatocellular carcinoma? A systematic review","volume":"111","author":"Dionisi","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.radonc.2014.11.033","article-title":"Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: A systematic review and meta-analysis","volume":"114","author":"Qi","year":"2015","journal-title":"Radiother. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijrobp.2012.08.043","article-title":"Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities","volume":"87","author":"Klein","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3389\/fphys.2013.00405","article-title":"Connexin and pannexin (hemi)channels in the liver","volume":"4","author":"Maes","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_10","first-page":"177","article-title":"Connexins and pannexins in liver damage","volume":"15","author":"Crespo","year":"2016","journal-title":"EXCLI J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.trsl.2015.05.005","article-title":"Connexin and pannexin signaling in gastrointestinal and liver disease","volume":"166","author":"Maes","year":"2015","journal-title":"Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.3748\/wjg.v10.i19.2785","article-title":"Are gap junction gene connexins 26, 32 and 43 of prognostic values in hepatocellular carcinoma? A prospective study","volume":"10","author":"Sheen","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_13","first-page":"1743","article-title":"Lentivirus-mediated shRNA interference of Cx26 suppresses epithelial mesenchymal transition and invasion of highly invasive hepatocellular carcinoma cells in vitro","volume":"34","author":"Yang","year":"2014","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/jrr\/rrs099","article-title":"Human cell responses to ionizing radiation are differentially affected by the expressed connexins","volume":"54","author":"Autsavapromporn","year":"2013","journal-title":"J. Radiat. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/bjc.2014.276","article-title":"Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced bystander effects","volume":"111","author":"Zhao","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"672571","DOI":"10.3389\/fcell.2021.672571","article-title":"Connexin26 Modulates the Radiosensitivity of Cutaneous Squamous Cell Carcinoma by Regulating the Activation of the MAPK\/NF-\u03baB Signaling Pathway","volume":"9","author":"Sun","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pbiomolbio.2007.03.011","article-title":"Connexin channel permeability to cytoplasmic molecules","volume":"94","author":"Harris","year":"2007","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00418-008-0432-9","article-title":"Expression of connexin 43 in normal canine testes and canine testicular tumors","volume":"130","author":"Ruttinger","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1165\/rcmb.2002-0281OC","article-title":"Cell-cell communication in heterocellular cultures of alveolar epithelial cells","volume":"29","author":"Isakson","year":"2003","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/mc.20268","article-title":"CpG site hypermethylation of E-cadherin and Connexin26 genes in hepatocellular carcinomas induced by a choline-deficient L-Amino Acid-defined diet in rats","volume":"46","author":"Tsujiuchi","year":"2007","journal-title":"Mol. Carcinog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1667\/0033-7587(2000)153[0508:RCOBAT]2.0.CO;2","article-title":"Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve","volume":"153","author":"Seymour","year":"2000","journal-title":"Radiat. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/35065000","article-title":"Mammalian MAP kinase signalling cascades","volume":"410","author":"Chang","year":"2001","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.cellsig.2003.08.006","article-title":"Redox regulates COX-2 upregulation and cell death in the neuronal response to cadmium","volume":"16","author":"Rockwell","year":"2004","journal-title":"Cell. Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1038\/sj.onc.1207556","article-title":"Mitogen-activated protein kinases in apoptosis regulation","volume":"23","author":"Wada","year":"2004","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/toxsci\/49.2.232","article-title":"Polycyclic aromatic hydrocarbons with bay-like regions inhibited gap junctional intercellular communication and stimulated MAPK activity","volume":"49","author":"Rummel","year":"1999","journal-title":"Toxicol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/mc.2940100407","article-title":"Changes in gap-junction permeability, phosphorylation, and number mediated by phorbol ester and non-phorbol-ester tumor promoters in rat liver epithelial cells","volume":"10","author":"Matesic","year":"1994","journal-title":"Mol. Carcinog."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1021\/jf051747h","article-title":"Chinese cabbage extracts and sulforaphane can protect H2O2-induced inhibition of gap junctional intercellular communication through the inactivation of ERK1\/2 and p38 MAP kinases","volume":"53","author":"Hwang","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.fct.2008.11.038","article-title":"Pterostilbene from Vitis coignetiae protect H2O2-induced inhibition of gap junctional intercellular communication in rat liver cell line","volume":"47","author":"Kim","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/carcin\/18.1.37","article-title":"Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells","volume":"18","author":"Upham","year":"1997","journal-title":"Carcinogenesis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1002\/hep.22049","article-title":"Biology and pathobiology of gap junctional channels in hepatocytes","volume":"47","author":"Vinken","year":"2008","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gong, G., Yuan, L., Cai, L., Ran, M., Zhang, Y., Gong, H., Dai, X., Wu, W., and Dong, H. (2014). Tetramethylpyrazine suppresses transient oxygen-glucose deprivation-induced connexin32 expression and cell apoptosis via the ERK1\/2 and p38 MAPK pathway in cultured hippocampal neurons. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105944"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.21873\/invivo.11387","article-title":"Magnolol Induces Apoptosis and Inhibits ERK-modulated Metastatic Potential in Hepatocellular Carcinoma Cells","volume":"32","author":"Kuan","year":"2018","journal-title":"In Vivo"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"BSR20171264","DOI":"10.1042\/BSR20171264","article-title":"Regorafenib inhibits tumor progression through suppression of ERK\/NF-\u03baB activation in hepatocellular carcinoma bearing mice","volume":"38","author":"Weng","year":"2018","journal-title":"Biosci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:42Z","timestamp":1760145942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,24]]},"references-count":33,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314644"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314644","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,24]]}}}