Journal of Endocrinological Investigation最新文献

{"title":"Leukocytosis in Cushing's syndrome persists post-surgical remission and could predict a lower remission prognosis in patients with Cushing's disease.","authors":"Hiba Masri-Iraqi, Yaron Rudman, Tzipora Shochat, Shiri Kushnir, Ilan Shimon, Maria Fleseriu, Amit Akirov","doi":"10.1007/s40618-025-02535-2","DOIUrl":"10.1007/s40618-025-02535-2","url":null,"abstract":"<p><strong>Context: </strong>Leukocytosis frequently noted in Cushing's syndrome (CS), along with other blood cell changes caused by direct and indirect cortisol effects.</p><p><strong>Objective: </strong>Assess baseline white blood cell (WBC) profile in CS patients compared to controls and WBC changes pre- and post-remission after surgical treatment for CS.</p><p><strong>Design: </strong>A comparative nationwide retrospective cohort study.</p><p><strong>Setting: </strong>Data from Clalit Health Services database.</p><p><strong>Patients: </strong>297 patients (mean age 51 ± 16.1 years, 73.0% women) with CS and 997 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS or adrenal cancer patients were excluded.</p><p><strong>Main outcome measure: </strong>Mean WBC, neutrophils, and neutrophil-to-lymphocyte ratio (NLR) two-years before and after pituitary or adrenal surgery. WBC and neutrophils are expressed as Kcells/µl.</p><p><strong>Results: </strong>At baseline, leukocytosis was observed in 21.5% of patients with CS vs. 8.9% of controls (P < 0.001). Patients with CS had significantly higher WBC (8.8 ± 2.88 vs. 7.54 ± 2.45, p < 0.0001), neutrophils (5.82 ± 2.38 vs. 4.48 ± 1.97, p < 0.0001), and NLR (3.37 ± 2.63 vs. 2.27 ± 1.86, p < 0.0001) compared to controls, regardless of pituitary or adrenal source of hypercortisolemia. Post-surgery, patients with CS experienced significant decreases in mean WBC (-0.57 ± 2.56, p < 0.0001), neutrophils (-0.84 ± 2.55, p < 0.0001), and NLR (-0.63 ± 2.7, p < 0.0001). Despite achieving disease remission, patients with CS still had higher WBC (8.11 ± 2.4 vs. 7.46 ± 2.17, p = 0.0004) and neutrophils (4.71 ± 2.10 vs. 4.41 ± 1.87, p = 0.03) compared to controls. Patients with CD and baseline leukocytosis had lower remission rate than those with normal WBC (36.7% vs. 63.9%, p = 0.01).</p><p><strong>Conclusions: </strong>At diagnosis, CS patients have elevated WBC, neutrophils, and NLR compared to controls. Remission does not normalize WBC levels in all patients, and baseline leukocytosis predicts a poorer remission prognosis in CD.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1217-1224"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early administration of romosozumab prevents rebound of bone resorption related to denosumab withdrawal in fractured post-menopausal women: a real-world prospective study.","authors":"Alberto Piasentier, Alessandro Fanti, Maria Francesca Birtolo, Walter Vena, Roberto Colle, Lucrezia Maria Silvana Gentile, Simona Jaafar, Antonio Carlo Bossi, Andrea G Lania, Gherardo Mazziotti","doi":"10.1007/s40618-025-02542-3","DOIUrl":"10.1007/s40618-025-02542-3","url":null,"abstract":"<p><strong>Purpose: </strong>The real-world effectiveness of switching from denosumab to romosozumab remains controversial. Sequential therapy with romosozumab was shown to be associated with inadequate suppression of bone resorption and there was anecdotal evidence of major osteoporotic fractures (MOFs) after transitioning from denosumab to romosozumab. This study evaluated the effects on bone resorption of early romosozumab administration 3 months after denosumab withdrawal in fractured women with post-menopausal osteoporosis.</p><p><strong>Methods: </strong>This prospective, single-center cohort study included 39 post-menopausal women with osteoporosis experiencing either MOFs or decrease in bone mineral density during long-term treatment with anti-resorptive drugs. Eighteen received romosozumab either 6 months (Group A) or 3 months (Group B) after their last denosumab dose, while 21 women switched from bisphosphonates to romosozumab and were enrolled as controls (Group C). Serum C-terminal telopeptide of type I collagen (CTX) levels were measured at baseline, 3 and 6 months.</p><p><strong>Results: </strong>All women of group A and 4 out of 8 women of group B showed a clinically significant increase of CTX values (i.e., change above the least significant change) (p = 0.023), which occurred earlier in group A as compared to group B. Moreover, 9/10 women of group A and 2/8 women of group B achieved values above the mean of reference range for pre-menopausal women (p = 0.013). In group C, serum CTX values did not change significantly during the follow-up. Two women in Group A experienced MOFs during the follow-up.</p><p><strong>Conclusions: </strong>Early romosozumab administration after denosumab withdrawal may control bone turnover rebound and possibly prevent incidence of fractures in post-menopausal osteoporosis.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1249-1256"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The paradoxical GH response at OGTT does not predict Pasireotide efficacy but matters for glucose metabolism.","authors":"G Occhi, G Voltan, S Chiloiro, A Bianchi, P Maffei, F Dassie, G Mantovani, G Del Sindaco, D Ferone, F Gatto, M Losa, S Cannavò, C Scaroni, F Ceccato","doi":"10.1007/s40618-025-02534-3","DOIUrl":"10.1007/s40618-025-02534-3","url":null,"abstract":"<p><strong>Purpose: </strong>A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development.</p><p><strong>Methods: </strong>we collected a multicenter Italian retrospective cohort of 59 patients treated with pasireotide for at least 3 months, all having GH profile from OGTT. IGF-1 normalization or at least 30% reduction at the last follow-up visit defined a responder patient.</p><p><strong>Results: </strong>Considering the entire cohort, median IGF-1 levels before pasireotide (available in 57 patients) were 1.38 times the upper limit of normal (ULN) in patients with large (median size 18 mm) and invasive (82%) adenomas after failure of fg-SRL treatment. After a 40-month median treatment, pasireotide effectively reduced IGF-1 ULN levels in 41 patients, 37 of whom achieving normalization, and 4 with a ≥ 30% reduction. Thirteen patients were classified as GH-Par. The median pasireotide duration, dosage, and efficacy (9/12 responder in the GH-Par group and 32/45 in the GH-NPar) were similar between groups. However, the occurrence of new-onset or worsening glucose metabolism alterations (GMAs) after pasireotide was more frequent in GH-NPar (from 37 to 80%; p < 0.001) compared to GH-Par patients (from 69 to 76%), likely due to the higher prevalence of pre-existing GMAs in the GH-Par group before starting pasireotide (p = 0.038).</p><p><strong>Conclusions: </strong>The GH-Par does not predict the response to pasireotide in acromegaly but can predict a worse metabolic profile.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1173-1183"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of androgen receptor on bone health in transgender adults: insights from the COMET study.","authors":"Chiara Ceolin, Alberto Scala, Maria Santa Rocca, Bianca Scagnet, Massimiliano Marton, Cristina Simonato, Chiara Ziliotto, Marina De Rui, Valentina Camozzi, Sandro Giannini, Daniela Basso, Giulia Musso, Alberto Ferlin, Giuseppe Sergi, Andrea Garolla","doi":"10.1007/s40618-024-02522-z","DOIUrl":"10.1007/s40618-024-02522-z","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms - known to affect bone density in the general population - has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population.</p><p><strong>Methods: </strong>This is an observational study involving 135 TGD and 107 cisgender participants. Collected data included hormonal profiles and phospho-calcium metabolism, bone geometry and density (Dual Energy X-ray Absorptiometry and peripheral Quantitative Computed Tomography). For the genetic study related to the AR, genomic DNA was extracted from peripheral blood leukocytes.</p><p><strong>Results: </strong>TGD individuals had lower BMD values compared to their cisgender peers. In a subgroup of 129 individuals (86 TGD and 43 cisgender), we assessed the length of the polymorphic tracts of the AR gene and observed no differences between the groups. AR polymorphisms showed significant correlations only with cortical BMD in both TGD and cisgender assigned females at birth (AFAB) individuals, and negative correlations with trabecular BMD in both cisgender men and women.</p><p><strong>Conclusions: </strong>Our study suggests that AR polymorphisms do not play a significant role in the low BMD values observed in TGD individuals at baseline. Further research is necessary to better understand the impact of factors such as lifestyle on the bone health of TGD individuals.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1237-1248"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Long noncoding RNA FAM111A-DT promotes aggressiveness of papillary thyroid cancer via activating NF-κB signaling.","authors":"Junxin Chen, Yue Chen, Rong Huang, Pengyuan Zhang, Zijun Huo, Yanbing Li, Haipeng Xiao, Hongyu Guan, Hai Li","doi":"10.1007/s40618-025-02538-z","DOIUrl":"10.1007/s40618-025-02538-z","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1137"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ccfDNA analysis for the classification of adrenocortical adenomas.","authors":"Mengjie Xu, David S Tourigny, Juliane Lippert, Ana Crastin, Silke Appenzeller, Miriam Asia, Oskar Podstawka, Gabrielle Smith, Yasir S Elhassan, Kassiani Skordilis, Alessandro Prete, Cristina L Ronchi","doi":"10.1007/s40618-025-02540-5","DOIUrl":"10.1007/s40618-025-02540-5","url":null,"abstract":"<p><strong>Background: </strong>Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.</p><p><strong>Materials and methods: </strong>We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.</p><p><strong>Results: </strong>Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.</p><p><strong>Conclusions: </strong>Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1207-1216"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the interplay of karyotype, hormones, sexuality, and body image perception in individuals with Turner syndrome.","authors":"Chiara Tarantino, Ludovica Vincenzi, Francesco Angelini, Alessandra Tomaselli, Francesco Carlomagno, Elena Rosato, Riccardo Pofi, Andrea Lenzi, Carlotta Pozza, Marianna Minnetti, Matteo Spaziani, Andrea M Isidori, Emilia Sbardella","doi":"10.1007/s40618-024-02521-0","DOIUrl":"10.1007/s40618-024-02521-0","url":null,"abstract":"<p><strong>Purpose: </strong>Most patients with Turner Syndrome (TS) require Hormone Replacement Therapy (HRT). Androgen levels could be compromised due to both ovarian insufficiency and HRT. Despite this, the association between androgen deficiency, sexual health, and body image perception remains underexplored in these patients. This study aimed to assess hormone levels, sexual function, and body image perception in women with TS, categorized by karyotype and HRT regimen.</p><p><strong>Methods: </strong>A cross-sectional analysis of 29 patients with TS was performed. Clinical, hormonal, and ultrasonographic pelvic parameters were evaluated. Sexual function and body image perception were measured using the Female Sexual Function Index (FSFI) and the Body Uneasiness Test (BUT) questionnaires.</p><p><strong>Results: </strong>The cohort included individuals with X chromosome monosomy (Group A), structural X chromosome alterations in some cell lines (Group B) or in all cell lines (Group C), and cells with 46, XX karyotype and monosomy (Group D). Group A and B compared to Group D displayed lower calculated free testosterone (p = 0.006, p = 0.032) and free androgen index levels (p = 0.007, p = 0.025). DHEA-S values differed between groups A and D (p = 0.043) and between groups A and C (p = 0.044). Sexual activity was reported by approximately half of patients (51.7%), with 57% of them presenting sexual dysfunction. Additionally, 44.8% exhibited possible body image disorder.</p><p><strong>Conclusions: </strong>This study acknowledges significant phenotypic differences linked to karyotype in women with TS, highlighting the prevalence of sexual dysfunction and body image dissatisfaction. These findings emphasize the importance of addressing sexual health and body image issues in patients with rare diseases, often neglected in clinical practice.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1225-1236"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Male osteoporosis: the impact of lifestyle, from nutrition to physical activity.","authors":"Giuseppe Defeudis, Ludovica Cardinali, Samaneh Eftekhariranjbar, Maria Chiara Massari, Silvia Migliaccio","doi":"10.1007/s40618-024-02517-w","DOIUrl":"10.1007/s40618-024-02517-w","url":null,"abstract":"<p><p>Male osteoporosis is an increasing worldwide pathological condition, characterized by an increased risk of fragility fractures, that is underestimated, underdiagnosed and undertreated. Prevention and treatment play a pivotal role in reducing fractures, and it is important to remember that therapeutic interventions include balanced nutrition and physical activity. Pharmacological treatments are the main and most effective tool to achieve numerous and decisive benefits in this population. Among these, testosterone replacement therapy, when allowed by circumstances and comorbidities, is useful. Anyway, the main goal is always to start from lifestyle, including nutrition and physical activity, plays a very important and crucial role. The many pieces of this puzzle, called lifestyle, need to be accurately collected and grouped carefully, in order to be able to have a broad picture of what needs to be integrated and what is sufficient for the ultimate purpose of enabling each individual man to have a sufficient basic health point. Thus, the purpose of this short narrative review is to highlight the preventive and therapeutic role of lifestyle components, particularly nutrition and physical activity, in males with osteoporosis. Finally, an evaluation of the impact of the main current diets used in recent years and the main physical activities as strategies for the safety of male bone health.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1075-1083"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBC9: a novel therapeutic target in papillary thyroid carcinoma.","authors":"Hui Zhang, Jingjing Wu, Huaiyuan Hu, Heng Tang, Kemeng Tan, Mengxue Hu, Genbao Zhu","doi":"10.1007/s40618-024-02523-y","DOIUrl":"10.1007/s40618-024-02523-y","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Despite the favorable prognosis in some patients, there remains a risk of lymph node metastasis and death in some patients. Therefore, new therapeutic strategies are required to improve PTC outcomes.</p><p><strong>Methods: </strong>In this study, we performed differential expression analysis using data from patients with PTC collected from the Cancer Genome Atlas program database, and prognostic analysis of differential genes. To understand the effects of ubiquitin-conjugating enzyme 9 (UBC9) on drug therapy, immunotherapy, immune relevance, and gene mutations in tumor cells of patients with PTC, we performed cancer drug susceptibility genomics, computed tumor immune dysfunction and exclusion, tertiary lymphoid tissues, cytolytic activity, immune infiltration, immune modulators, genomic signature differences, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Moreover, we investigated the function of UBC9 in tumor cells using a knockdown assay.</p><p><strong>Results: </strong>UBC9 expression level was significantly elevated in the tumor tissues of patients with PTC, and in vitro experiments demonstrated that UBC9 knockdown inhibited tumor proliferation and migration and promoted apoptosis. UBC9 is closely linked to immunity in PTC, and UBC9 may be a potential therapeutic target.</p><p><strong>Conclusions: </strong>Our study demonstrated that UBC9 is a novel therapeutic target for PTC and may be a potential strategy for its treatment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1101-1119"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA FAM111A-DT promotes aggressiveness of papillary thyroid cancer via activating NF-κB signaling.","authors":"Junxin Chen, Yue Chen, Rong Huang, Pengyuan Zhang, Zijun Huo, Yanbing Li, Haipeng Xiao, Hongyu Guan, Hai Li","doi":"10.1007/s40618-025-02531-6","DOIUrl":"10.1007/s40618-025-02531-6","url":null,"abstract":"<p><strong>Purpose: </strong>Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the tumorigenesis and progression of various cancers. However, the functional roles of lncRNAs in papillary thyroid cancer (PTC) remain unclear. In this study, we investigated the functional role of the lncRNA FAM111A-DT in PTC progression and the underlying mechanisms.</p><p><strong>Methods: </strong>Different expression levels of lncRNAs in PTC were compared via analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses and qRT‒PCR were used to investigate the expression of FAM111A-DT in PTC. Cell proliferation was measured via CCK8, EdU, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. Apoptosis was detected via flow cytometry. RNA sequencing, qRT‒PCR, Western blot, immunofluorescence and dual-luciferase reporter assays were performed to assess the underlying mechanisms involved.</p><p><strong>Results: </strong>FAM111A-DT was highly expressed in PTC and associated with poor prognosis, thyroid dedifferentiation, various clinical features and the BRAF^V600E mutation in PTC patients. Overexpression of FAM111A-DT enhanced the proliferation, migration and invasion of PTC cells while reducing their degree of apoptosis. The NF-κB signaling pathway was activated in FAM111A-DT-overexpressing PTC cells. The NF-κB inhibitor PDTC attenuated the promotive effects of FAM111A-DT on aggressive phenotypes and NF-κB pathway activity in PTC cells.</p><p><strong>Conclusion: </strong>FAM111A-DT is upregulated in PTC, and its expression is associated with poor clinical outcomes. FAM111A-DT plays an oncogenic role by, at least partially, activating the NF-κB signaling pathway.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"1121-1136"},"PeriodicalIF":5.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}