Molecular and Cellular Biochemistry最新文献

{"title":"High glucose facilitates hepatocellular carcinoma cell proliferation and invasion via WTAP-mediated HK2 mRNA stability.","authors":"Yongshen Niu, Siying Jia, Xuelian Xiao, Kangsheng Tu, Qingguang Liu","doi":"10.1007/s11010-025-05235-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05235-w","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is one of the most common cancers, and diabetes is a risk factor for hepatocarcinogenesis. N6-methyladenosine (m6A) methyltransferase WT1-associated protein (WTAP) is highly expressed in HCC and contributes to tumor progression. However, its role in high glucose-driven HCC progression remains unclear. The m6A quantitative assay was used to detect the m6A modification level. The levels of mRNAs and proteins were detected by qPCR, Western blot, and immunohistochemistry. CCK-8, colony formation, EdU, and transwell assays were used to detect HCC cell proliferation, invasion, and migration. Immunoprecipitation and CHX assays were used to reveal the regulatory effect of high glucose on WTAP. An RNA degradation experiment was used to explore WTAP's regulation of HK2 mRNA. To demonstrate the effect of high glucose on HCC growth in vivo, a diabetic mouse model was constructed, and HCC cells were subcutaneously injected. High glucose prominently increased the global level of m6A in HCC cells. Interestingly, high glucose upregulated WTAP protein rather than mRNA expression. We found that WTAP expression was significantly upregulated in HCC tissues, especially in tumor tissues of diabetic patients. WTAP knockdown markedly attenuated high glucose-induced abilities of HCC cell proliferation, colony formation, migration, and invasion. Meanwhile, WTAP overexpression significantly enhanced the malignant behaviors of HCC cells under low glucose conditions. High glucose reduced the ubiquitination of WTAP, thereby inhibiting its proteasomal and lysosomal degradation. Phosphorylated ERK (p-ERK) was required for high glucose-mediated WTAP stability. WTAP knockdown prominently abrogated high glucose-induced global m6A levels and HK2 expression in HCC cells. WTAP positively regulated HK2 expression by increasing mRNA stability. HK2 overexpression remarkably reversed the suppressive effects of WTAP knockdown on HCC cells. HK2 knockdown prominently abolished the promoting role of WTAP in HCC cells. Importantly, the growth of HCC cells in diabetic mice was significantly faster than that in control mice, which was prominently attenuated by WTAP knockdown. Our study demonstrated that high glucose decreased WTAP degradation and maintained its protein level by activating ERK phosphorylation. WTAP promoted HCC cell proliferation, colony formation, migration, and invasion by stabilizing HK2 mRNA.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization underlying IFN-α2 treatment in polycythemia vera: a transcriptomic overview.","authors":"Fang-Fang Liu, Ke Li","doi":"10.1007/s11010-025-05238-7","DOIUrl":"https://doi.org/10.1007/s11010-025-05238-7","url":null,"abstract":"<p><p>Polycythemia vera (PV) is the most common chronic myeloproliferative neoplasm (MPN) in adults. Pegylated interferon-α2 (IFN-α2) is an effective and safe drug for the treatment of PV. However, the mechanisms of its action in PV are still not fully understood. Using the WGCNA and Limma algorithm, we found a subset of IFN-α2 sensitive genes and four gene co-expression modules. Meanwhile, we also found 820 genes were differentially expressed in PV compared with healthy controls. By integrating the above results, several differentially expressed genes (DEGs) that were up- or down-regulated in PV but showed opposite alterations in the IFN-α2-treated group were found. These genes were mainly related to three types of biological processes (metal ion homeostasis, metabolic/catabolic process, and Jak-STAT signaling pathway), the dysfunctions of which were prevalent in PV. Moreover, we applied another threshold-free analysis method to compare global gene expression between IFN-α2 treated PV, PV, and control groups. Results showed the transcriptome changes of PV versus controls were negatively correlated with that of IFN-α2 treated versus untreated PV, indicating IFN-α2 treatment could partially reverse the dysregulated gene expression profile due to PV pathology. In summary, interferon may alleviate the progression of PV through multiple pathways. The findings may be of assistance in understanding the molecular basis underlying this treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omic high-throughput strategies across-species identified potential key diagnostic, prognostic, and therapeutic targets for atherosclerosis under high glucose conditions.","authors":"Zhida Shen, Meng Zhao, Jiangting Lu, Huanhuan Chen, Yicheng Zhang, Songzan Chen, Zhaojing Wang, Meihui Wang, Xianglan Liu, Guosheng Fu, He Huang","doi":"10.1007/s11010-024-05097-8","DOIUrl":"10.1007/s11010-024-05097-8","url":null,"abstract":"<p><p>Diabetes is a well-known risk factor for atherosclerosis (AS), but the underlying molecular mechanism remains unknown. The dysregulated immune response is an important reason. High glucose is proven to induce foam cell formation under lipidemia situations in clinical patients. Exploring the potential regulatory programs of accelerated foam cell formation stimulated by high glucose is meaningful. Macrophage-derived foam cells were induced in vitro, and high-throughput sequencing was performed. Coexpression gene modules were constructed using weighted gene co-expression network analysis (WGCNA). Highly related modules were identified. Hub genes were identified by multiple integrative strategies. The potential roles of selected genes were further validated in bulk-RNA and scRNA datasets of human plaques. By transfection of the siRNA, the role of the screened gene during foam cell formation was further explored. Two modules were found to be both positively related to high glucose and ox-LDL. Further enrichment analyses confirmed the association between the brown module and AS. The high correlation between the brown module and macrophages was identified and 4 hub genes (Aldoa, Creg1, Lgmn, and Pkm) were screened. Further validation in external bulk-RNA and scRNA revealed the potential diagnostic and therapeutic value of selected genes. In addition, the survival analysis confirmed the prognostic value of Aldoa while knocking down Aldoa expression alleviated the foam cell formation in vitro. We systematically investigated the synergetic effects of high glucose and ox-LDL during macrophage-derived foam cell formation and identified that ALDOA might be an important diagnostic, prognostic, and therapeutic target in these patients.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1785-1805"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of high-sensitivity C-reactive protein and hematologic-inflammatory indices with risk of cardiovascular diseases: a population-based study with partial least squares structural equation modeling approach.","authors":"Somayeh Ghiasi Hafezi, Rana Kolahi Ahari, Maryam Saberi-Karimian, Zahra Eslami Giski, Amin Mansoori, Gordon A Ferns, Mahmoud Ebrahimi, Alireza Heidari-Bakavoli, Mohsen Moohebati, Sara Yousefian, Farnaz Farrokhzadeh, Habibollah Esmaily, Majid Ghayour-Mobarhan","doi":"10.1007/s11010-024-05122-w","DOIUrl":"10.1007/s11010-024-05122-w","url":null,"abstract":"<p><p>Partial least squares structural equation modeling is a simple approach that may be used to determine the factors associated with diseases. In the current study, we aimed to explore the most associated high-sensitivity C-reactive protein (hs-CRP) as well as hematologic-inflammatory indices for the risk of cardiovascular disease (CVD). A total of 7362 healthy (non-CVD) participants aged 35-65 years old from baseline investigation were evaluated in the Phase 2 follow-up. Of these, 1022 individuals were found to have CVDs in the second phase (10-year follow-up) of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. We used partial least squares structural equation modeling to develop a prediction model for association of CVD risk factors and hs-CRP as well as hematologic-inflammatory indices in the study population. According to the study, age had the most significant impact on the presence of CVD. Increasing in age by one unit raises the risk of CVD by 0.166. Also, serum hs-CRP was found to have the second-highest impact on CVD; increasing in age by one unit raises the risk of CVD by 0.042. The study also discovered a strong and significant correlation between red cell distribution width (RDW) and CVD. Moreover, the study found that several factors such as hemoglobin (HGB), neutrophil (NEUT), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet-to-lymphocyte ratio (PLR) have indirect effects on CVD that are mediated by hs-CRP while controlling for age, sex and social-economic factors. Generally, the results showed that age, hs-CRP, and RDW were the most important risk factors on CVD.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1909-1918"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of exercise in modulating plasma heat shock protein 27 levels: insights for exercise immunology and cardiovascular health.","authors":"Fábio Lera Orsatti, Augusto Corrêa de Queiroz Freitas, Anna Victória Bernardes E Borges, Alexia Souza Santato, Claudio de Oliveira Assumpção, Markus Vinicius Campos Souza, Marcos Vinicius da Silva, Cláudio Lera Orsatti","doi":"10.1007/s11010-024-05089-8","DOIUrl":"10.1007/s11010-024-05089-8","url":null,"abstract":"<p><p>Cardiovascular disease is one of the leading causes of mortality worldwide, primarily driven by atherosclerosis, a chronic inflammatory condition contributing significantly to fatalities. Various biological determinants affecting cardiovascular health across different age and sex groups have been identified. In this context, recent attention has focused on the potential therapeutic and preventive role of increasing circulating levels of heat shock protein 27 (plasma HSP27) in combating atherosclerosis. Plasma HSP27 is recognized for its protective function in inflammatory atherogenesis, offering promising avenues for intervention and management strategies against this prevalent cardiovascular ailment. Exercise has emerged as a pivotal strategy in preventing and managing cardiovascular disease, with literature indicating an increase in plasma HSP27 levels post-exercise. However, there is limited understanding of the impact of exercise on the release of HSP27 into circulation. Clarifying these aspects is crucial for understanding the role of exercise in modulating plasma HSP27 levels and its potential implications for cardiovascular health across diverse populations. Therefore, this review aims to establish a more comprehensive understanding of the relationship between plasma HSP27 and exercise.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1381-1401"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into non-coding RNAS: biogenesis, function and their potential regulatory roles in acute kidney disease and chronic kidney disease.","authors":"Shulin Li, Wanru Hu, Luoxiang Qian, Dong Sun","doi":"10.1007/s11010-024-05083-0","DOIUrl":"10.1007/s11010-024-05083-0","url":null,"abstract":"<p><p>Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1287-1304"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic prospects of microRNAs derived from mesenchymal stem cell extracellular vesicles in rheumatoid arthritis: a comprehensive overview.","authors":"Armin Akbarzadeh, Mohammad Hadi Gerami, Majid Reza Farrokhi, Shima Shapoori, Morteza Jafarinia","doi":"10.1007/s11010-024-05082-1","DOIUrl":"10.1007/s11010-024-05082-1","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammatory joint damage. Recent studies have focused on the significance of microRNAs (miRNAs) in the pathogenesis of RA. Mesenchymal stem cells (MSCs) have emerged as a potential therapeutic option for RA based on their regenerative and immunomodulatory properties. MSCs release extracellular vesicles (EVs) containing miRNAs that can modulate immune and inflammatory responses. This article provides a comprehensive overview of the current evidence on the existence of various MSCs-derived miRNAs involved in the pathophysiology, characterization, and treatment of RA. An overview of the miRNA profiles in MSC-EVs is provided, along with an examination of their impact on various cell types implicated in RA pathogenesis, including synovial fibroblasts, macrophages, and T cells. Furthermore, the therapeutic capability of MSC-EVs for miRNA-based therapies in RA is discussed. In total, this review can present an extensive view of the complex interaction between EVs and MSC-derived miRNAs in RA and thus suggest valuable strategies for developing new therapeutic approaches to target this debilitating disease.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1275-1286"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-15a-5p from cardiomyocytes promotes myocardial fibrosis.","authors":"Feng Cao, Zhe Li, Wenmao Ding, Chuan Qv, Hongyi Zhao","doi":"10.1007/s11010-024-05080-3","DOIUrl":"10.1007/s11010-024-05080-3","url":null,"abstract":"<p><p>The emergence of myofibroblasts is a key step in myocardial fibrosis, but the trigger for the transformation of cardiac fibroblasts into myofibroblasts remains not entirely clear. Exosomes play a key role between cardiomyocytes and cardiac fibroblasts. Here, we not only investigated the relationship between exosomes derived from angiotensin (Ang)-II-treated cardiomyocytes and cardiac fibroblasts, the underlying mechanisms were also explored. Ang-II-treated C57 male mice and mouse cardiac fibroblasts were employed for in vivo and in vitro experiments, respectively. Transmission electron microscopy nanoparticle tracking analysis, and western blot of CD9, CD63, CD81 were performed to identify exosomes; QRT-PCR was performed to detect miR-15a-5p expression; luciferase reporter assay was employed to determine the interaction between miR-15a-5p and dyrk2; western blot was performed to examine the protein levels of fibrosis markers; Counting Kit-8 was performed to determine cell viability; HE and Masson staining were performed to assess the pathological changes of myocardial tissues. MiR-15a-5p expression was found up-regulated in serum of myocardial fibrosis patients, serum and myocardial tissues of Ang-II-treated mice, and Ang-II-treated cardiomyocytes. Mechanically, exosomes from Ang-II-treated cardiomyocytes shuttled miR-15a-5p to cardiac fibroblasts, where miR-15a-5p dephosphorylated NFAT by targeting dyrk2 to promote cell viability and elevated the protein levels of α-smooth muscle actin, collagen type 1 α1 and collagen type 3 α1, thus promoting myocardial fibrosis. This study identified a novel molecular target for anti-fibrotic therapeutic interventions.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1701-1713"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting BRD4 to attenuate RANKL-induced osteoclast activation and bone erosion in rheumatoid arthritis.","authors":"Changyao Wang, Han Zhang, Xiangyu Wang, Xiao Ma, Jian Zhang, Yongtao Zhang","doi":"10.1007/s11010-024-05073-2","DOIUrl":"10.1007/s11010-024-05073-2","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause destruction of cartilage and bone's extracellular matrix. Bromodomain 4 (BRD4), as a transcriptional and epigenetic regulator, plays a key role in cancer and inflammatory diseases. While, the role of BRD4 in bone destruction in RA has not been extensively reported. Our study aimed to investigate the effect of BRD4 on the bone destruction in RA and, further, its mechanism in the pathogenesis of the disease. In this study, receiving approval from the Ethical Committee of the Affiliated Hospital of Qingdao University, we evaluated synovial tissues from patients with RA and OA for BRD4 expression through advanced techniques such as immunohistochemistry, quantitative real-time PCR (qRT-PCR), and Western blotting. We employed a collagen-induced arthritis (CIA) mouse model to assess the therapeutic efficacy of the BRD4 inhibitor JQ1 on disease progression and bone destruction, supported by detailed clinical scoring and histological examinations. Further, in vitro osteoclastogenesis assays using RAW264.7 macrophages, facilitated by TRAP staining and resorption pit assays, provided insights into the mechanistic effects of JQ1 on osteoclast function. Statistical analysis was rigorously conducted using SPSS, applying Kruskal-Wallis, one-way ANOVA, and Student's t-tests to validate the data. In our study, we found that BRD4 expression significantly increased in the synovial tissues of RA patients and the ankle joints of CIA mice, with JQ1, a BRD4 inhibitor, effectively reducing inflammation, arthritis severity (p < 0.05), and bone erosion. Treatment with JQ1 not only improved bone mass and structural integrity in CIA mice but also downregulated osteoclast-related gene expression and the RANKL/RANK signaling pathway, indicating a suppression of osteolysis. Furthermore, in vitro assays demonstrated that JQ1 markedly inhibited osteoclast differentiation and function, underscoring the pivotal role of BRD4 in osteoclastogenesis and its potential as a target for therapeutic intervention in RA-induced bone destruction. Our study concludes that targeting BRD4 with the inhibitor JQ1 significantly mitigates inflammation and bone destruction in rheumatoid arthritis, suggesting that inhibition of BRD4 may be a potential therapeutic strategy for the treatment of bone destruction in RA.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1669-1684"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircXPO6 promotes breast cancer progression through competitively inhibiting the ubiquitination degradation of c-Myc.","authors":"Aiqi Xu, Xi Li, Qiaoting Cai, Ciqiu Yang, Mei Yang, Hongfei Gao, Minyi Cheng, Xianzhe Chen, Fei Ji, Hailin Tang, Kun Wang","doi":"10.1007/s11010-024-05093-y","DOIUrl":"10.1007/s11010-024-05093-y","url":null,"abstract":"<p><p>The number of breast cancer (BC) patients is increasing year by year, which is severely endangering to human life and health. c-Myc is a transcription factor, studies have shown that it is a very significant factor in tumor progression, but how it is regulated in BC is still not well understood. Here, we used the RIP microarray sequencing to confirm circXPO6, which had a high affinity with c-Myc and highly expressed in triple-negative breast cancer (TNBC) tissues and cells. CircXPO6 overexpression promoted tumor growth in vivo and in vitro. Furthermore, circXPO6 largely promoted the expression of genes related to glucose metabolism, such as GLUT1, HK2, and MCT4 in TNBC cells. Finally, high levels of circXPO6 expression were found to be closely associated with malignant pathological factors, such as tumor size, lymph node metastasis, TNM staging, and histopathological grading of TNBC. Mechanistically, circXPO6 interacted with c-Myc to prevent speckle-type POZ-mediated c-Myc ubiquitination and degradation, thus promoting TNBC progression. Through the regulation of c-Myc-mediated signal transduction, circXPO6 plays a key role in TNBC progresses. This discovery can provide new ideas for TNBC molecular targeted therapy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"1731-1745"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}