{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T15:32:45Z","timestamp":1793287965682,"version":"4.5.0"},"reference-count":74,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2022A1515111044"],"award-info":[{"award-number":["2022A1515111044"]}]},{"name":"National Natural Science Foundation of China","award":["82222051"],"award-info":[{"award-number":["82222051"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82573910"],"award-info":[{"award-number":["82573910"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Guangzhou Basic and Applied Basic Research Foundation","award":["202201011018"],"award-info":[{"award-number":["202201011018"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      The coexistence of\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>V600E<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">telomerase reverse transcriptase<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">TERT)<\/jats:italic>\n                      promoter alterations has been reported to cooperatively upregulate TERT expression and is well recognized as a biomarker for aggressive thyroid cancer. However, the mechanism underlying their synergistic effect remains elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      TERT-interacting proteins were identified via immunoprecipitation (IP) and mass spectrometry and validated by Co-IP. DDX21 expression was detected in 60 paired thyroid cancer and adjacent normal tissues, and the function of DDX21 in thyroid cancer was explored\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      . Integrated analyses of RNA-seq, ChIP-seq, and Ribo-seq assays were conducted to elucidate the molecular mechanisms. BRAF\/MEK inhibitors and\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>V600E<\/jats:sup>\n                      <\/jats:italic>\n                      overexpression were used to investigate the regulation of DDX21 by\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      mutation.\n                      <jats:italic toggle=\"yes\">In silico<\/jats:italic>\n                      analysis, ChIP, and luciferase reporter assays were used to identify the transcription factors binding to DDX21 promoter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      DDX21 interacted with TERT to regulate ribosomal RNA (rRNA) transcription by affecting the binding of Pol I to rDNA. DDX21 is upregulated in thyroid cancer, and DDX21 knockdown decreased the expression of multiple cancer hallmark genes and suppressed cell proliferation, colony formation, cell migration, and invasion of thyroid cancer cells. GABPA bound to the promoter of\n                      <jats:italic toggle=\"yes\">DDX21<\/jats:italic>\n                      , and knockdown of GABPA or GABPB1 suppressed\n                      <jats:italic toggle=\"yes\">DDX21<\/jats:italic>\n                      promoter activity and transcription. Pharmacological inhibition of the MAPK pathway in\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      -mutant cancer cells decreased the expression of GABPA, GABPB1, and DDX21.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>V600E<\/jats:sup>\n                      <\/jats:italic>\n                      upregulates expression of DDX21 through the MEK\/ERK\/GABP axis. DDX21, in turn, interacts with TERT to promote rRNA transcription and modulate the expression of multiple cancer hallmark genes, driving the malignant progression of thyroid cancer. These findings suggest that DDX21 acts as a mediator to bridge the crosstalk between\n                      <jats:italic toggle=\"yes\">\n                        BRAF\n                        <jats:sup>V600E<\/jats:sup>\n                      <\/jats:italic>\n                      and TERT and may serve as a therapeutic target for patients with thyroid cancer harboring\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                      alterations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256261417697","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T13:17:57Z","timestamp":1769087877000},"page":"305-319","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["DDX21 Links\n                    <i>\n                      BRAF\n                      <sup>V600E<\/sup>\n                    <\/i>\n                    and TERT to Promote Thyroid Cancer Progression"],"prefix":"10.1177","volume":"36","author":[{"given":"Mengke","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."},{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lefan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Sang","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubin","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haipeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 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