{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:30:43Z","timestamp":1787725843013,"version":"build-2784847793"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to characterize molecular subtypes of Papillary thyroid carcinoma (PTC) and identify novel therapeutic targets and potential therapeutic compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed integrative analysis of TCGA data, including consensus clustering, mutational profiling, copy number variation (CNV) analysis, functional enrichment (GO and GSEA), and immune microenvironment assessment (CIBERSORT). Validation utilized GEO datasets. The biological function of Plectin (PLEC) was investigated through expression analysis (TCGA, GEO, qRT-PCR and IHC), association with clinical parameters, and functional experiments such as siRNA knockdown or overexpression of PLEC in TPC-1 and B-CPAP cell lines assessing cell growth, proliferation, apoptosis, and migration both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Drug candidates targeting PLEC were screened (DGIdb and DrugMap) and validated via molecular docking, dynamics simulations (RMSD, RMSF and Rg), and rescue experiments. Favorable biosafety was tested by ELISA kits and H&amp;amp;E staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Consensus clustering revealed four stable molecular subtypes (A1-A4) with distinct mutational landscapes (e.g., prevalent\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations (59%), subtype-specific alterations in\n                      <jats:italic>CAND1\/PCDH11X<\/jats:italic>\n                      (A1) and\n                      <jats:italic>PTEN<\/jats:italic>\n                      (A4)), CNV gains (e.g., A1: 2p16.1\/19p13.3), and immune features (A3 enriched in immune pathways). PLEC is up-regulated in PTC tissues compared with non-tumor thyroid tissues and was associated with lymph node metastasis, histological type, and residual tumor status in TCGA-THCA. Knockdown of PLEC significantly suppressed PTC cell growth, proliferation, and migration while inducing apoptosis. Whereas PLEC overexpression partially reversed these phenotypes. Among FDA-approved drugs predicted to target PLEC, Troglitazone exhibited the lowest binding affinity (-7.5 kcal\/mol). Troglitazone\u2019s anti-tumor effects (inhibiting proliferation\/migration, inducing apoptosis) were partially reversed by PLEC overexpression, suggesting that PLEC may participate in Troglitazone-associated anti-PTC effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify PLEC as a candidate molecule associated with aggressive PTC phenotypes and provide preliminary evidence supporting its biological relevance, although larger independent cohorts are required to validate its clinical significance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1789251","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:03:46Z","timestamp":1787724226000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of plectin as a druggable target in papillary thyroid carcinoma: therapeutic potential of troglitazone"],"prefix":"10.3389","volume":"17","author":[{"given":"Yi-Chen","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]},{"name":"Departments of General Surgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Digestive Diagnosis and Treatment, First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tie-Feng","family":"Shi","sequence":"additional","affiliation":[{"name":"Departments of General Surgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Fu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1725077","article-title":"Lymphatic metastasis of papillary thyroid carcinoma: mechanism and clinicopathological physiology","volume":"16","author":"Liu","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1512417","article-title":"Papillary thyroid carcinoma with Hashimoto's thyroiditis: impact and correlation","volume":"16","author":"Yao","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23572","article-title":"Let-7a-5p abrogates progression of papillary thyroid carcinoma cells by decreasing nuclear receptor subfamily 6 group a member 1-mediated lipogenesis","volume":"38","author":"Zhao","year":"2024","journal-title":"J Biochem Mol Toxicol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13046-025-03341-7","article-title":"Single-cell transcriptomics analysis reveals that the tumor-infiltrating B cells determine the indolent fate of papillary thyroid carcinoma","volume":"44","author":"Li","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000001875","article-title":"Artificial intelligence-based multi-modal multi-tasks analysis reveals tumor molecular heterogeneity, predicts preoperative lymph node metastasis and prognosis in papillary thyroid carcinoma: a retrospective study","volume":"111","author":"Yu","year":"2025","journal-title":"Int J Surg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2025.110706","article-title":"Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: a game-changing meta-analysis","volume":"205","author":"Toraih","year":"2025","journal-title":"Radiother Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9959649","article-title":"Risk and prognostic factors for Braf(V600e) mutations in papillary thyroid carcinoma","volume":"2022","author":"Wei","year":"2022","journal-title":"BioMed Res Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106966","article-title":"The clinical and immune features of Cd14 in colorectal cancer identified via large-scale analysis","volume":"88","author":"Chen","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202101_24635","article-title":"The progression of pancreatic cancer cells is promoted by a long non-coding RNA Lucat1 by activating Akt phosphorylation","volume":"25","author":"Cao","year":"2021","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1526051","article-title":"Gut microbiota derived metabolite trimethylamine N-oxide influences prostate cancer progression via the P38\/Hmox1 pathway","volume":"15","author":"Zhou","year":"2024","journal-title":"Front Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-020-01166-8","article-title":"Comparison of molecular methods and Braf immunohistochemistry (Ve1 clone) for the detection of Braf V600e mutation in papillary thyroid carcinoma: a meta-analysis","volume":"14","author":"Parker","year":"2020","journal-title":"Head Neck Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.240208","article-title":"Mechanics of cell sheets: Plectin as an integrator of cytoskeletal networks","volume":"15","author":"Outla","year":"2025","journal-title":"Open Biol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13578-025-01349-2","article-title":"Plectin, a novel regulator in migration, invasion and adhesion of ovarian cancer","volume":"15","author":"Bai","year":"2025","journal-title":"Cell Biosci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-025-02113-1","article-title":"High matrix stiffness accelerates migration of hepatocellular carcinoma cells through the integrin Beta1-plectin-F-actin axis","volume":"23","author":"Wang","year":"2025","journal-title":"BMC Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2025.101549","article-title":"Unraveling the oncogenic characteristics of the cytolinker, plectin, in esophageal squamous cell carcinoma","volume":"19","author":"Qiao","year":"2025","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-025-02001-8","article-title":"Imaging cell surface plectin in Pdac patients - a first-in-human phase 0 study report","volume":"27","author":"Dimastromatteo","year":"2025","journal-title":"Mol Imaging Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/0113892010284407240212110745","article-title":"Recent developments in nanotechnology and immunotherapy for the diagnosis and treatment of pancreatic cancer","volume":"26","author":"Sindhi","year":"2025","journal-title":"Curr Pharm Bio\/Technol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000915","article-title":"Microrna-216b regulates cell proliferation, invasion and cycle progression via interaction with cyclin T2 in gastric cancer","volume":"31","author":"Chen","year":"2020","journal-title":"Anticancer Drugs"},{"key":"B19","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1097\/CAD.0000000000000975","article-title":"Upregulated long noncoding RNAs Linc02163 and Fezf1-As1 exert oncogenic roles in colorectal cancer","volume":"32","author":"Tian","year":"2021","journal-title":"Anticancer Drugs"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/09603271221138971","article-title":"Overexpression of lncRNA A2m-As1 inhibits cell growth and aggressiveness via regulating the miR-587\/bone morphogenetic protein 3 axis in lung adenocarcinoma","volume":"41","author":"Guo","year":"2022","journal-title":"Hum Exp Toxicol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116295","article-title":"Angelica sinensis polysaccharide suppresses the Wnt\/beta-catenin-mediated Malignant biological behaviors of breast cancer cells via the miR-3187-3p\/Pcdh10 axis","volume":"225","author":"Cai","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112873","article-title":"Circgnao1 suppresses hepatocellular carcinoma progression and metastasis via sponging miR-182-5p and regulating Foxo1 expression","volume":"140","author":"Ju","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001614","article-title":"Nedd8-specific protease 1 deficiency as a novel driver of hepatoblastoma development through dysregulation of the Cand1-Nedd8 pathway","author":"Zapata-Pavas","year":"2025","journal-title":"Hepatology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1007\/s00109-024-02450-8","article-title":"Pcdh11x mutation as a potential biomarker for immune checkpoint therapies in lung adenocarcinoma","volume":"102","author":"Liu","year":"2024","journal-title":"J Mol Med (Berl)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41698-026-01371-8","article-title":"Impact of Braf, Tert, and novel mutations on the efficacy of Lenvatinib for advanced papillary thyroid cancer: a national genomic database analysis","volume":"10","author":"Sato","year":"2026","journal-title":"NPJ Precis Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"884","DOI":"10.3390\/cells15100884","article-title":"Roles of Stat3 and Stat family proteins and their signaling pathways in thyroid cancer","volume":"15","author":"Masaki","year":"2026","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41419-025-07593-1","article-title":"Pla2g7 promotes immune evasion of bladder cancer through the Jak-Stat-Pdl1 axis","volume":"16","author":"Peng","year":"2025","journal-title":"Cell Death Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3718","article-title":"Inhibition of antiviral drug Cidofovir on proliferation of human papillomavirus-infected cervical cancer cells","volume":"12","author":"Yang","year":"2016","journal-title":"Exp Ther Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.152447","article-title":"Clodronate-induced cell apoptosis in human thyroid carcinoma is mediated via the P2 receptor signaling pathway","volume":"330","author":"Yang","year":"2009","journal-title":"J Pharmacol Exp Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-02086","article-title":"Abemaciclib plus fulvestrant in advanced breast cancer after progression on Cdk4\/6 inhibition: results from the phase III Postmonarch trial","volume":"43","author":"Kalinsky","year":"2025","journal-title":"J Clin Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.05.097","article-title":"Niclosamide induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in human thyroid cancer in vitro","volume":"92","author":"Yu","year":"2017","journal-title":"BioMed Pharmacother"},{"key":"B32","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12935-024-03319-z","article-title":"The troglitazone derivative Ep13 disrupts energy metabolism through respiratory chain complex I inhibition in breast cancer cells and potentiates the antiproliferative effect of glycolysis inhibitors","volume":"24","author":"Muller","year":"2024","journal-title":"Cancer Cell Int"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.1516","article-title":"Adjuvant zoledronate therapy for women with breast cancer-effective treatment or fool's gold","volume":"7","author":"Desnoyers","year":"2021","journal-title":"JAMA Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.178343","article-title":"Ppargamma ligands activate the ion channel Trpa1","volume":"1008","author":"Guenther","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"10968","DOI":"10.3390\/ijms262210968","article-title":"Effects of inhibitors of the activity of the circulating renin-angiotensin system on the growth and proliferation of endometrial cancer cells","volume":"26","author":"Delforce","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2026.153611","article-title":"High concentrations of Gw9508 enhance sperm velocity in mice via peroxisome proliferator-activated receptor gamma","volume":"812","author":"Moriyama","year":"2026","journal-title":"Biochem Biophys Res Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13205110","article-title":"Ppargamma targets-derived diagnostic and prognostic index for papillary thyroid cancer","volume":"13","author":"Kim","year":"2021","journal-title":"Cancers (Basel)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1789251\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:03:48Z","timestamp":1787724228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1789251\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2026.1789251"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1789251","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"article-number":"1789251"}}