Molecular Oncology最新文献_第8页

Somatic mutational landscape in von Hippel-Lindau familial hemangioblastoma. von Hippel-Lindau家族性血管母细胞瘤的体细胞突变景观。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-03-23 DOI: 10.1002/1878-0261.70228

Maja Dembic, Anne Nørremølle, Lilian Bomme Ousager, Lars van Brakel Andersen, Marie Louise Mølgaard Binderup, Mads Thomassen

{"title":"Somatic mutational landscape in von Hippel-Lindau familial hemangioblastoma.","authors":"Maja Dembic, Anne Nørremølle, Lilian Bomme Ousager, Lars van Brakel Andersen, Marie Louise Mølgaard Binderup, Mads Thomassen","doi":"10.1002/1878-0261.70228","DOIUrl":"10.1002/1878-0261.70228","url":null,"abstract":"Von Hippel-Lindau disease (vHL) predisposes to tumor development, mainly clear cell renal carcinoma and hemangioblastoma. The underlying cause is germline variants in the VHL gene, with tumorigenesis thought to require additional somatic 'second-hit' events that most commonly include loss of 3p. However, the precise mechanisms of vHL-related tumor development remain incompletely understood. Genomic investigations of familial hemangioblastoma may help elucidate the early steps of tumorigenesis and contribute to improved disease prediction, biomarker discovery, and therapeutic strategies. We performed whole exome sequencing on 22 familial hemangioblastomas from 7 patients representing 5 unrelated families, and with 4 different causative VHL genotypes. The tumors exhibited low overall mutational burden but showed frequent loss of heterozygosity on chromosome 3 or 3p and single nucleotide variants in the VHL region. Variants were significantly enriched in genes associated with GABAergic and serotonergic neuronal cell types, as well as in pathways regulating cell cycle and neurogenesis. These findings suggest that, in addition to VHL loss, dysregulation of neuronal differentiation programs and cell cycle control may play important roles in hemangioblastoma tumorigenesis.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2023-2039"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503946","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}

引用次数: 0

Interaction of HS1BP3 with cortactin modulates TKS5 localisation, cell secretion and cancer malignancy. HS1BP3与接触素的相互作用调节TKS5的定位、细胞分泌和肿瘤恶性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-04-10 DOI: 10.1002/1878-0261.70248

Arja Arnesen Løchen, Kristiane Søreng, Chiara Veroni, Laura Trachsel-Moncho, Nagham Asp, Robin Gaupset, Lars Gustav Lyckander, Helene Knævelsrud, Lars Eftang, Anne Simonsen

{"title":"Interaction of HS1BP3 with cortactin modulates TKS5 localisation, cell secretion and cancer malignancy.","authors":"Arja Arnesen Løchen, Kristiane Søreng, Chiara Veroni, Laura Trachsel-Moncho, Nagham Asp, Robin Gaupset, Lars Gustav Lyckander, Helene Knævelsrud, Lars Eftang, Anne Simonsen","doi":"10.1002/1878-0261.70248","DOIUrl":"10.1002/1878-0261.70248","url":null,"abstract":"The HCLS1-Binding Protein 3 (HS1BP3) interacts with the SH3 domain of cortactin (CTTN), a protein that contributes to a malignant phenotype in cancers. Here, we demonstrate that high expression of HS1BP3 is associated with reduced survival for gastric adenocarcinoma and triple negative breast carcinoma patients and that HS1BP3 is specifically upregulated in these cancers. We mapped the HS1BP3-cortactin interaction site to the third proline-rich region (PRR3.1) of HS1BP3 and show that this interaction is important for cancer cell proliferation, extracellular matrix degradation and secretion. HS1BP3 expression was found to correlate with expression of the invadopodia scaffold protein TKS5 and we show that the localisation of TKS5 inside multivesicular endosomes is increased in cells expressing an HS1BP3 PRR3.1 mutant. Overall, our results highlight the importance of the direct interaction between HS1BP3 and cortactin in cancer development by regulating cell proliferation, secretion and invasion, which may provide an explanation for the negative correlation between HS1BP3 levels and the survival of gastric adenocarcinoma and triple negative breast cancer patients.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"1986-2007"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645786","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}

引用次数: 0

ESR1 methylation and ESR1 mutations in circulating tumor cells (CTCs) and paired plasma-cfDNA of advanced breast cancer patients: A feasibility proof-of-concept study. 晚期乳腺癌患者循环肿瘤细胞（ctc）和配对血浆cfdna中的ESR1甲基化和ESR1突变：一项可行性概念验证研究

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-05-27 DOI: 10.1002/1878-0261.70254

Dimitra Stergiopoulou, Athina Markou, Eleonora Nicolo, Mara S Serafini, Qiang Zhang, Youbin Zhang, Lorenzo Gerratana, Andrew A Davis, Huiping Liu, William J Gradishar, Carolina Reduzzi, Massimo Cristofanilli, Evi Lianidou

{"title":"ESR1 methylation and ESR1 mutations in circulating tumor cells (CTCs) and paired plasma-cfDNA of advanced breast cancer patients: A feasibility proof-of-concept study.","authors":"Dimitra Stergiopoulou, Athina Markou, Eleonora Nicolo, Mara S Serafini, Qiang Zhang, Youbin Zhang, Lorenzo Gerratana, Andrew A Davis, Huiping Liu, William J Gradishar, Carolina Reduzzi, Massimo Cristofanilli, Evi Lianidou","doi":"10.1002/1878-0261.70254","DOIUrl":"10.1002/1878-0261.70254","url":null,"abstract":"Endocrine resistance is a complex phenomenon, including alterations of the ESR1 gene. The aim of this study was to simultaneously analyze ESR1 promoter methylation and ESR1 hotspot mutations in circulating tumor cells (CTCs) and paired plasma-circulating tumor DNA (ctDNA) from patients with estrogen receptor-positive (ER+) advanced breast cancer (BC). We retrospectively analyzed samples from 42 ER+ advanced BC patients characterized for CTCs and ctDNA at Northwestern University. CTCs were enumerated using the CellSearch® system, while ctDNA was analyzed with the Guardant360 NGS platform. Genomic DNA from CellSearch-enriched CTC fractions was amplified and analyzed using the ESR1-NAPA assay. ESR1 methylation analysis was performed in 34 samples. ESR1 mutations were detected in 59.5% CTC-derived samples, a significantly higher proportion than in paired plasma ctDNA (29.6%). ESR1 methylation was observed in 26.5% patients. Concurrent ESR1 mutations and methylation were identified in six cases, suggesting combined genetic and epigenetic mechanisms of endocrine resistance. Overall, CTC-derived genomic DNA showed higher sensitivity for detecting ESR1 mutations than plasma ctDNA, supporting the potential value of CTC analysis for characterizing endocrine resistance in advanced BC.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2102-2113"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042828","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}

引用次数: 0

Circulating tumor cell viability during and after radiotherapy mirrors treatment response in cancer patients. 放疗期间和放疗后循环肿瘤细胞活力反映了癌症患者的治疗反应。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-04-23 DOI: 10.1002/1878-0261.70261

Yvonne Goy, Jana Löptien, Cornelia Coith, Afroditi Nanou, Katharina Hintelmann, Pinnschmidt Hans, Cordula Petersen, Klaus Pantel, Sabine Riethdorf, Kerstin Borgmann, Harriet Wikman

{"title":"Circulating tumor cell viability during and after radiotherapy mirrors treatment response in cancer patients.","authors":"Yvonne Goy, Jana Löptien, Cornelia Coith, Afroditi Nanou, Katharina Hintelmann, Pinnschmidt Hans, Cordula Petersen, Klaus Pantel, Sabine Riethdorf, Kerstin Borgmann, Harriet Wikman","doi":"10.1002/1878-0261.70261","DOIUrl":"10.1002/1878-0261.70261","url":null,"abstract":"The response to radiotherapy (RT) is influenced by the individual DNA repair capacity of both the tumor cells and the host. In this study, we assessed whether circulating tumor cell (CTC) enumeration, kinetics, and CTC viability (i.e., the apoptotic rate) could provide a more accurate tool for monitoring and stratifying the RT response. We analyzed CTCs and tumor-derived extracellular vesicles (tdEVs) during RT in 71 lung (n = 35) and breast (n = 36) cancer patients receiving RT treatment for brain (n = 54) and bone (n = 19) metastases. The DNA repair capacity of the host was assessed by ex vivo irradiation of peripheral blood mononuclear cells (PBMCs). RT treatment did not seem, in most cases, to cause a short-term release of CTCs. We found that both the number and apoptotic rate of CTCs before and after RT treatment is a powerful indicator of poor prognosis. Additionally, the fraction of apoptotic CTCs correlated with RT response and patient outcome. This study demonstrated that the RT response is associated with tumor-specific traits, which can be accessed via easily accessible liquid biopsy approaches.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2040-2053"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776154","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}

引用次数: 0

Adaptor protein CIN85 potentiates the motility of osteosarcoma cells via the Akt/mTOR and MMP2-COL3A1 axis. 适配蛋白CIN85通过Akt/mTOR和MMP2-COL3A1轴增强骨肉瘤细胞的运动性。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-08-01 Epub Date: 2026-04-17 DOI: 10.1002/1878-0261.70245

Iryna Horak, Iva Staniczková Zambo, Matěj Přikryl, Peter Múdry, Danica Zapletalová, Jarmila Navrátilová, Jiří Navrátil, Jan Šmarda, Liudmyla Drobot, Petr Beneš, Lucia Knopfová

{"title":"Adaptor protein CIN85 potentiates the motility of osteosarcoma cells via the Akt/mTOR and MMP2-COL3A1 axis.","authors":"Iryna Horak, Iva Staniczková Zambo, Matěj Přikryl, Peter Múdry, Danica Zapletalová, Jarmila Navrátilová, Jiří Navrátil, Jan Šmarda, Liudmyla Drobot, Petr Beneš, Lucia Knopfová","doi":"10.1002/1878-0261.70245","DOIUrl":"10.1002/1878-0261.70245","url":null,"abstract":"Osteosarcoma is the most common malignant bone tumor, primarily affecting adolescents and young adults. Patients with metastases have a low survival rate, making the identification of prognostic markers crucial. The adaptor protein CIN85 is involved in various signaling pathways that regulate cell differentiation, adhesion, and motility. Its overexpression is associated with poor prognosis in multiple cancers. However, the role of CIN85 in osteosarcoma progression has not yet been explored. This study shows that CIN85 expression is higher in osteosarcoma than in normal bone tissue and further increased in metastatic lesions relative to primary tumors. CIN85 overexpression increases cell migration and Matrigel invasion, whereas silencing CIN85 suppresses these behaviors. Functional annotation and enrichment analyses of the CIN85-driven transcriptome suggest that CIN85 regulates migration, adhesion, and extracellular matrix organization in osteosarcoma. CIN85 affects MMP2 and COL3A1 gene expression and activates Akt/mTOR signaling. Knockdown of MMP2 and COL3A1 or pharmacological inhibion of Akt/mTOR signaling abrogates CIN85-induced motility. This study demonstrates that elevated CIN85 expression contributes to osteosarcoma migration and metastasis, highlighting its potential as a therapeutic target.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":"2085-2101"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717411","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}

引用次数: 0

PANoptosis in the pathogenesis of myelodysplastic syndromes. PANoptosis在骨髓增生异常综合征发病机制中的作用。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-07-24 DOI: 10.1002/1878-0261.70309

Rohit Thalla, Jyoti Lamichhane, Cameron Lewis, Peter Breslin, Jiwang Zhang

{"title":"PANoptosis in the pathogenesis of myelodysplastic syndromes.","authors":"Rohit Thalla, Jyoti Lamichhane, Cameron Lewis, Peter Breslin, Jiwang Zhang","doi":"10.1002/1878-0261.70309","DOIUrl":"10.1002/1878-0261.70309","url":null,"abstract":"Myelodysplastic syndromes (MDS) are a heterogeneous group of pre-leukemic diseases marked by ineffective bone marrow (BM) hematopoiesis, peripheral cytopenia, morphologic dysplasia, and an increased risk of leukemic transformation. Increased programmed cell death (PCD) of hematopoietic stem/progenitor cells (HSPCs) and its associated inflammatory BM microenvironment have been speculated to be one of the major causes of ineffective hematopoiesis. PANoptosis is a collective term for three types of PCD: pyroptosis, apoptosis, and necroptosis. All three are mediated by a very large protein complex called a PANoptosome, composed of the key mediators of the three types of PCD. We reported that the diseased cells in MDS with genetic abnormalities, especially spliceosome mutations, show aberrant hypersensitivity to PANoptotic stimuli. Our study suggests that increased PANoptosis of BM HSPCs is one of the reasons for the ineffective hematopoiesis in MDS patients, and targeting PANoptosis may be a novel treatment strategy for MDS. Here we summarize recent advances in research into PANoptosis and discuss the potential role of PANoptosis in the pathogenesis of MDS. We discuss the potential mechanisms for targeting PANoptotic pathways to treat MDS.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579494","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}

引用次数: 0

Circulating microRNA signatures of cachexia and cancer in Canis familiaris as a comparative oncology model for human disease. 犬恶病质和癌症的循环microRNA特征作为人类疾病的比较肿瘤学模型。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-07-22 DOI: 10.1002/1878-0261.70293

Soon-Seok Park, Kyongman An, Gyeonghwa Kim, Soo-Nyun Choi, Hong-Ki Lee, Keun Hur, Kyu-Shik Jeong

{"title":"Circulating microRNA signatures of cachexia and cancer in Canis familiaris as a comparative oncology model for human disease.","authors":"Soon-Seok Park, Kyongman An, Gyeonghwa Kim, Soo-Nyun Choi, Hong-Ki Lee, Keun Hur, Kyu-Shik Jeong","doi":"10.1002/1878-0261.70293","DOIUrl":"10.1002/1878-0261.70293","url":null,"abstract":"Cachexia, a severe muscle-wasting syndrome, lacks objective biomarkers for early detection. This study aimed to identify circulating microRNA signatures for cachexia and cancer in senior dogs, a comparative oncology model for human disease. Serum microRNA expression was quantified in a cohort of 25 dogs, clinically classified by cachexia and cancer status. We identified a distinct signature for cachexia, with significant downregulation of miR-15a, miR-15b, miR-16, and miR-140. Circulating miR-16 emerged as the most robust individual biomarker for cachexia (AUC = 0.899). Furthermore, a sex-specific analysis revealed that miR-140 was significantly lower in female dogs with cancer compared to noncancer controls (P = 0.045), consistent with a sex- and disease-specific dual suppression mechanism involving estrogen receptor signaling and cachexia-driven systemic inflammation (corrected AUC = 0.667). These findings suggest circulating microRNAs as promising, noninvasive biomarkers for canine cachexia and highlight miR-140 as a candidate sex-specific biomarker for female cancers, warranting validation in larger cohorts. This work reinforces the value of the domestic dog as a spontaneous model for translational biomarker discovery.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549855","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}

引用次数: 0

Pharmacological chromatin remodeling enhances response to estrogen therapy in ER⁺ breast cancer. 药物染色质重塑增强雌激素受体阳性乳腺癌对雌激素治疗的反应。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-07-17 DOI: 10.1002/1878-0261.70307

Anneka L Johnson Thomas, Barbara Karakyriakou, Patricia C Muskus, Alyssa M Roberts, Justin Rendleman, Alexa Warren, Hanxu Lu, Kimberly A Birmingham, Malone K Friedman, Abigail E Goen, Huijuan Yang, Owen M Wilkins, Fred W Kolling, Eugene Demidenko, Julie M Jorns, Brock C Christensen, Todd W Miller

{"title":"Pharmacological chromatin remodeling enhances response to estrogen therapy in ER+ breast cancer.","authors":"Anneka L Johnson Thomas, Barbara Karakyriakou, Patricia C Muskus, Alyssa M Roberts, Justin Rendleman, Alexa Warren, Hanxu Lu, Kimberly A Birmingham, Malone K Friedman, Abigail E Goen, Huijuan Yang, Owen M Wilkins, Fred W Kolling, Eugene Demidenko, Julie M Jorns, Brock C Christensen, Todd W Miller","doi":"10.1002/1878-0261.70307","DOIUrl":"10.1002/1878-0261.70307","url":null,"abstract":"Estrogen therapy elicits clinical benefit in ~ 30% of patients with endocrine-resistant estrogen receptor (ER)-positive breast cancer, but its mechanism of action and strategies to increase efficacy remain unclear. Estrogen therapy can induce ER transcriptional hyperactivation and DNA damage; we postulated that such damage could be exacerbated by epigenetic dysregulation via inhibition of histone deacetylases (HDACi). We evaluated the effects of 17b-estradiol and HDACi in three types of ER+ breast cancer models: Cells adapted to growth following long-term estrogen deprivation; cells engineered to overexpress exogenous ER that confers endocrine resistance; mice bearing endocrine-resistant patient-derived xenografts. Assay endpoints included apoptosis, growth, DNA damage, histone post-translational modification, levels of ER-regulated transcripts and encoded proteins, cell cycle and replication status, and genome-wide chromatin accessibility, ER binding, and transcriptional profiles. Entinostat treatment increased histone acetylation and chromatin accessibility. Combination treatment with E2 and entinostat inhibited cell growth and induced apoptosis in ER-overexpressing models. E2 and entinostat induced DNA damage as single agents and in combination. These agents synergized against tumor models, offering HDACi as a strategy to enhance efficacy of estrogen therapy.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471802","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}

引用次数: 0

Epigenetic silencing of the liver-specific lncRNA LUNAR promotes liver cancer progression via NOTCH activation. 表观遗传沉默肝脏特异性lncRNA LUNAR通过NOTCH激活促进肝癌进展。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-07-12 DOI: 10.1002/1878-0261.70301

Se Ha Jang, Hyung Seok Kim, Geum Ok Baek, Moon Gyeong Yoon, Su In Lee, Jee-Yeong Jeong, Ji Eun Han, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun

{"title":"Epigenetic silencing of the liver-specific lncRNA LUNAR promotes liver cancer progression via NOTCH activation.","authors":"Se Ha Jang, Hyung Seok Kim, Geum Ok Baek, Moon Gyeong Yoon, Su In Lee, Jee-Yeong Jeong, Ji Eun Han, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun","doi":"10.1002/1878-0261.70301","DOIUrl":"10.1002/1878-0261.70301","url":null,"abstract":"While long noncoding RNAs (lncRNAs) play critical roles in hepatocellular carcinoma (HCC) pathogenesis, the regulatory mechanisms governing liver-specific lncRNAs remain poorly defined. Here, we systematically analyzed staging-specific transcriptomic datasets to identify functionally relevant lncRNAs involved in HCC progression. We identified a liver-specific lncRNA, termed LUNAR (Liver-specific Upregulated Non-coding RNA as Down-Regulator in HCC), reflecting its high expression in normal liver tissue and its functional role in restraining tumor progression in HCC. Analyses across multiple independent patient cohorts revealed that LUNAR expression correlated with clinical outcomes in HCC. Functional assays demonstrated that restoration of LUNAR expression suppressed cell migration, invasion, and in vivo metastasis, without affecting cell proliferation. Mechanistically, LUNAR overexpression was associated with attenuation of NOTCH signaling, while its downregulation in tumors was linked to epigenetic silencing via promoter hypermethylation. Collectively, these findings identify LUNAR as a liver-enriched, epigenetically regulated lncRNA with metastasis-restraining functions. This therefore supports the potential of LUNAR as a tissue-associated biomarker and therapeutic target in HCC.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13399082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430796","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}

引用次数: 0

CEACAM1 participation in breast cancer progression. CEACAM1参与乳腺癌进展。

IF 4.5 2区医学

Molecular Oncology Pub Date : 2026-07-10 DOI: 10.1002/1878-0261.70306

Mykola Lyndin, Irina Kube-Golovin, Anatolii Romaniuk, Gunther Wennemuth

{"title":"CEACAM1 participation in breast cancer progression.","authors":"Mykola Lyndin, Irina Kube-Golovin, Anatolii Romaniuk, Gunther Wennemuth","doi":"10.1002/1878-0261.70306","DOIUrl":"10.1002/1878-0261.70306","url":null,"abstract":"Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in human cells and undergoes marked alterations during tumorigenesis. However, its functional significance in invasive breast cancer (BC) remains insufficiently understood. In this study, CEACAM1 expression patterns in invasive BC tissues were analyzed and correlated with the proliferative index (PI) of the tumor cells. To assess isoform-specific functional effects and identify CEACAM1-responsive genes involved in key proliferation-associated pathways, MCF-7 cells were transfected with either CEACAM1 short cytoplasmic domain isoform (CEACAM1-4S) or CEACAM1 long cytoplasmic domain isoform (CEACAM1-4L). BC tissues exhibited substantial heterogeneity in CEACAM1 expression, which correlated with the PI of the tumor cells. Functional in vitro studies demonstrated that the CEACAM1-4L isoform exclusively suppresses cell proliferation. Transcriptome and protein-level analyses revealed that CEACAM1-4L regulates the expression of key mediators involved in cell cycle control, apoptosis, extracellular matrix organization, and growth factor-dependent signaling pathways. These findings highlight the biological significance of CEACAM1-4L isoform in BC, its potential diagnostic relevance for patient stratification, as well as its possible consideration in future therapeutic approaches.","PeriodicalId":18764,"journal":{"name":"Molecular Oncology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422562","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}

引用次数: 0