{"title":"Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers.","authors":"Songyun Zhao, Hua Yu, Zihao Li, Wanying Chen, Kaibo Liu, Hao Dai, Gaoyi Wang, Zibing Zhang, Jiaheng Xie, Yucang He, Liqun Li","doi":"10.1186/s13062-025-00628-9","DOIUrl":"10.1186/s13062-025-00628-9","url":null,"abstract":"<p><p>Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients' quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to deeply analyze the cellular heterogeneity of the skin on the feet ofDFU patients and the transcriptomic characteristics of endothelial cells, aiming to identify key cell populations and genes associated with the healing and progression of DFU. The study found that endothelial cells from DFU patients exhibited significant transcriptomic differences under various conditions, particularly in signaling pathways related to inflammatory responses and angiogenesis. Through trajectory analysis and cell communication research, we revealed the key role of endothelial cell subsets in the development of DFU and identified multiple important gene modules associated with the progression of DFU. Notably, the promoting effect of the SH3BGRL3 gene on endothelial cell proliferation, migration, and angiogenic capabilities under high glucose conditions was experimentally verified, providing a new potential target and theoretical basis for the treatment of DFU. This study not only enhances the understanding of the pathogenesis ofDFU but also provides a scientific basis for the development ofnew therapeutic strategies.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"34"},"PeriodicalIF":5.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690528","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}
Biology DirectPub Date : 2025-03-21DOI: 10.1186/s13062-025-00626-x
Daniele Andrean, Francesco Da Ros, Mario Mazzucato, Morten Gram Pedersen, Roberto Visentin
{"title":"Doxorubicin PK/PD modeling in multiple myeloma: towards in silico trials.","authors":"Daniele Andrean, Francesco Da Ros, Mario Mazzucato, Morten Gram Pedersen, Roberto Visentin","doi":"10.1186/s13062-025-00626-x","DOIUrl":"10.1186/s13062-025-00626-x","url":null,"abstract":"<p><p>Doxorubicin (DOXO) is a well-known chemotherapy drug, which is widely used in the treatment of Multiple Myeloma (MM), a treatable but not curable type of blood cancer. Here, we propose a pharmacokinetics and pharmacodynamics (PK/PD) simulation environment, aimed at facilitating the optimization of DOXO treatment regimens in MM treatment. The resulting model has a transparent mechanistic structure, which facilitates its use and interpretation. The simulator was developed using a combination of experimental and modeling techniques, starting from in vitro PK/PD experiments conducted on MM cells. In our previous work, we carefully developed a PK model for DOXO in MM cells by fitting experimental data. We now devise a PD model from in vitro data investigating the effect of different concentrations of DOXO on cell growth and death in MM cell populations. The PK model is extended to enable a clear mechanistic link between the PK and the PD models, hence providing a complete PK/PD simulator. We show how the mathematical model can be exploited to simulate different DOXO administration protocols with different dosages, repetitions and exposure times, thus, making it possible to explore the effect of a wide range of treatment protocols easily.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"33"},"PeriodicalIF":5.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676823","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}
Biology DirectPub Date : 2025-03-20DOI: 10.1186/s13062-025-00604-3
Sergey E Parfenyev, Alexandra A Daks, Oleg Y Shuvalov, Olga A Fedorova, Nikolay B Pestov, Tatyana V Korneenko, Nickolai A Barlev
{"title":"Dualistic role of ZEB1 and ZEB2 in tumor progression.","authors":"Sergey E Parfenyev, Alexandra A Daks, Oleg Y Shuvalov, Olga A Fedorova, Nikolay B Pestov, Tatyana V Korneenko, Nickolai A Barlev","doi":"10.1186/s13062-025-00604-3","DOIUrl":"10.1186/s13062-025-00604-3","url":null,"abstract":"<p><p>It is generally accepted that ZEB1 and ZEB2 act as master regulators of the epithelial-mesenchymal transition, which arguably is the key mechanism of metastasis. Accordingly, they are deemed as negative predictors of the survival of cancer patients by promoting the emergence of secondary foci of the disease. Paradoxically, in some types of cancer types the opposite effect is observed, i.e. ZEB1 and ZEB2 are associated with better prognosis for cancer patients. In this review, we discuss the hypothesis that the tumorigenic effects of ZEB1/ZEB2 can be different in various tissues depending on the initial status of these proteins in the corresponding healthy tissues. Emerging evidence suggests that ZEB1 and ZEB2 are constitutively expressed in several healthy tissues, performing vital functions. Consequently, reducing the expression of ZEB1 and ZEB2 could negatively affect these tissues causing various diseases, including cancer. Finally, the dualistic role of ZEB1 and ZEB2 as immune modulators and their effect on tumor microenvironment is also discussed.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"32"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668929","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}
Biology DirectPub Date : 2025-03-19DOI: 10.1186/s13062-025-00609-y
Maheswary Muniandy, Sakari Joenväärä, Birgitta W van der Kolk, Tiialotta Tohmola, Hanna Haltia, Sina Saari, Antti Hakkarainen, Jesper Lundbom, Juho Kuula, Per-Henrik Groop, Jaakko Kaprio, Sini Heinonen, Risto Renkonen, Kirsi H Pietiläinen
{"title":"Plasma N-Glycoproteomics in monozygotic twin pairs discordant for body mass index reveals an obesity signature related to inflammation and iron metabolism.","authors":"Maheswary Muniandy, Sakari Joenväärä, Birgitta W van der Kolk, Tiialotta Tohmola, Hanna Haltia, Sina Saari, Antti Hakkarainen, Jesper Lundbom, Juho Kuula, Per-Henrik Groop, Jaakko Kaprio, Sini Heinonen, Risto Renkonen, Kirsi H Pietiläinen","doi":"10.1186/s13062-025-00609-y","DOIUrl":"10.1186/s13062-025-00609-y","url":null,"abstract":"<p><strong>Background: </strong>N-glycosylation is a complex, post-translational modification which influences protein function and is sensitive to physiological changes. Obesity is associated with alterations in protein function; however, little is known about the glycoproteome in obesity beyond observations of association with types and structures of selected glycopeptides. Most often, due to technical challenges, glycan composition and structure information are missing. Here, we combined label-free data-independent proteomics and targeted quantitative glycoproteomics to study N-glycosylation of plasma proteins in obesity. Using a monozygotic twin study design, we controlled for genetic variation and focused only on the acquired effects of obesity.</p><p><strong>Methods: </strong>Using plasma samples of 48 monozygotic twin pairs discordant for BMI (intrapair difference > 2.5 kg/m<sup>2</sup>), we identified using mass spectrometry, differential protein and glycopeptide levels between heavier and leaner co-twins. We used a within-twin paired analysis model and considered p < 0.05 as significant.</p><p><strong>Results: </strong>We identified 48 protein and 33 N-glycosylation expression differences (p < 0.05) between co-twins. These differences occurred either both in the protein expression and glycoprotein (sometimes in opposing directions) or independently from each other. Haptoglobin protein was upregulated (Fold Change = 1.10, p = 0.001) in heavier co-twins along with seven upregulated glycan compositions at N-glycosylation site Asn241. The complement protein C3 was upregulated (Fold Change = 1.08, p = 0.014) along with one upregulated glycopeptide at Asn85. Additionally, many glycopeptides were upregulated despite non-significant differences in protein-backbone plasma levels.</p><p><strong>Conclusion: </strong>Differential protein expression related to cholesterol biosynthesis and acute phase signalling as well as N-glycosylation of proteins related to iron metabolism and inflammation can be linked to acquired obesity.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"31"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662581","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}
Biology DirectPub Date : 2025-03-14DOI: 10.1186/s13062-025-00621-2
Xiuyun Duan, Li Zhang, Keyu Liu, Kaiyin Guo, Yingnan You, Hailin Jia, Shan Zhou, Bo Han
{"title":"Macrophage-derived SPP1 exacerbate myocardial injury by interacting with fibroblasts in viral myocarditis.","authors":"Xiuyun Duan, Li Zhang, Keyu Liu, Kaiyin Guo, Yingnan You, Hailin Jia, Shan Zhou, Bo Han","doi":"10.1186/s13062-025-00621-2","DOIUrl":"10.1186/s13062-025-00621-2","url":null,"abstract":"<p><strong>Background: </strong>Viral myocarditis (VMC) is an inflammatory myocardial condition triggered by viral infections which involves pathogenic-related damage and immune-mediated damage. However, the precise immunopathogenic mechanisms underlying VMC remain elusive.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on mouse hearts during the acute phase of CVB3-induced VMC. After manually annotating cell types, functional analyses of macrophage were performed by cell ratio changes, customized gene set module scoring and CellPhoneDB. Utilizing indirect co-culture experiments in vitro, the effects of macrophage-derived SPP1 on cardiac fibroblasts were investigated. Depletion of macrophages and inhibition of SPP1 expression in mice were carried out to study the effects of macrophage-derived SPP1 on cardiac function, inflammation levels, and myocardial injury in mice with VMC.</p><p><strong>Results: </strong>Our data revealed that macrophages are the major immune cells which infiltrate the heart during the acute phase of VMC, particularly a macrophage subpopulation which highly expresses Spp1 (Spp1<sup>+</sup> macrophages) and exhibited characteristics of peripheral blood monocytes. Spp1<sup>+</sup> macrophages communicate extensively with fibroblasts during VMC, and that SPP1 promotes fibroblast conversion to an inflammatory phenotype with high Ccl2/Ccl7 expression. This in turn increases monocyte chemotaxis to the heart. Besides, a partial depletion of macrophages in the early stages of VMC attenuated myocardial inflammation and myocardial injury in mice. Inhibition of SPP1 reduced cardiac macrophage infiltration, attenuated myocardial inflammation, and improved cardiac function in VMC mice.</p><p><strong>Conclusion: </strong>Our findings suggested that Spp1<sup>+</sup> macrophages could self-recruit, and macrophage-derived SPP1 exacerbated myocardial immune injury by promoting high Ccl2/Ccl7 expression in fibroblasts. Our study advances understandings of VMC pathogenesis, and provides novel insight into potential immunotherapies for VMC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"30"},"PeriodicalIF":5.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633671","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}
Biology DirectPub Date : 2025-03-10DOI: 10.1186/s13062-025-00618-x
Jun Du, Jiaqi Liu, Xiaoya Wang, Xiaowu Wang, Yu Ma, Sipan Zhang, Zilin Li, Jipeng Ma, Jincheng Liu
{"title":"The role of estrogen in the sex difference for the risk factors of heart failure with preserved ejection fraction.","authors":"Jun Du, Jiaqi Liu, Xiaoya Wang, Xiaowu Wang, Yu Ma, Sipan Zhang, Zilin Li, Jipeng Ma, Jincheng Liu","doi":"10.1186/s13062-025-00618-x","DOIUrl":"10.1186/s13062-025-00618-x","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) is a major subtype of heart failure, primarily characterized by a normal or mildly reduced left ventricular ejection fraction along with left ventricular diastolic dysfunction. Recent studies have shown that the prevalence of HFpEF is higher in women than that in men, particularly in postmenopausal women. Concurrently, it has been observed that the incidence of risk factors contributing to HFpEF (such as obesity, hypertension, diabetes, and atrial fibrillation) also notably increases post-menopause, affecting the incidence of HFpEF. This review aimed to examine the relationship between estrogen and risk factors associated with HFpEF, clarifying the underlying mechanisms through which estrogen affects these risk factors from epidemiological and pathophysiological perspectives. This review also provides a comprehensive understanding of the association between estrogen and the risk factors for HFpEF, thus helping explore potential targets for HFpEF treatment.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"28"},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596128","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}
Biology DirectPub Date : 2025-03-10DOI: 10.1186/s13062-025-00625-y
Francesca Bellinazzo, Irene Manders, Bas Heidemann, Manuel Aguirre Bolanos, Evelien Stouten, Jacqueline Busscher, Dolores Abarca, Froukje van der Wal, Marcelo Carnier Dornelas, Gerco C Angenent, Marcel Proveniers, Harm Nijveen, Richard G H Immink
{"title":"Differential growth and flowering capacity of tulip bulbs and the potential involvement of PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS (PEBPs).","authors":"Francesca Bellinazzo, Irene Manders, Bas Heidemann, Manuel Aguirre Bolanos, Evelien Stouten, Jacqueline Busscher, Dolores Abarca, Froukje van der Wal, Marcelo Carnier Dornelas, Gerco C Angenent, Marcel Proveniers, Harm Nijveen, Richard G H Immink","doi":"10.1186/s13062-025-00625-y","DOIUrl":"10.1186/s13062-025-00625-y","url":null,"abstract":"<p><strong>Background: </strong>Tulipa gesneriana reproduces vegetatively by the development of bulb clusters from axillary meristems in the scales of a mother bulb. While part of the daughter bulbs in a cluster develop into large, flowering bulbs, others stay small and vegetative under the same environmental conditions. This study aims to investigate how these different developmental fates are orchestrated.</p><p><strong>Results: </strong>RNA-seq analysis revealed that the overall transcriptomic landscape of the two types of daughter bulbs does not differ substantially, but follows a similar trajectory over time. Nonetheless, the expression levels of genes related to proliferation already differ at early development stages. Surprisingly, at a later stage, transcriptomic changes related to flower induction are detectable in flowering as well as non-flowering bulbs, with some quantitative differences. However, genes linked with floral organ development are differentially expressed, as well as negative regulators of flowering and more basal metabolic processes. In search for the molecular determinants of daughter bulb size and developmental fate, we investigated members of the PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN (PEBP) gene family as candidates. Tulip FLOWERING LOCUS T1 (TgFT1), TgFT2, and TgFT3 are expressed in leaves and leaf-like organs of the mother plant, and their encoded proteins interact with the TCP transcription factor TEOSINTE BRANCHED1 (TgTB1). Therefore, we suggest that these three genes act as 'bulbigens', meaning regulators of axillary meristem outgrowth and hence, daughter bulb size. Furthermore, we found that TgFT2 and TgFT4 could constitute the main florigens in tulips, because of their expression pattern and the binding of their encoding proteins to the bZIP transcription factor FD (TgFD). Moreover, Arabidopsis lines ectopically expressing TgFT2 or TgFT4 flower significantly earlier than the wild type.</p><p><strong>Conclusions: </strong>Differences in the developmental fate of tulip daughter bulbs are established early during development and are linked with differences in cell division and metabolism. The activity of members of the PEBP family, known for their role in flowering and storage organ formation in geophytes, appeared to be associated with the transcriptional switches observed during daughter bulb development. This points towards a functional role of these proteins in governing developmental trajectories underlying the mode of reproduction.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"29"},"PeriodicalIF":5.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596111","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}
Biology DirectPub Date : 2025-03-05DOI: 10.1186/s13062-025-00620-3
Enshuang Guo, Lei Li, Jiankun Yang, Yongjian Zhou, Lu Bai, Weiwei Zhu, Qiuyue Hu, Huifen Wang, Hongqiang Liu
{"title":"HOXB4/METTL7B cascade mediates malignant phenotypes of hepatocellular carcinoma through TKT m6A modification.","authors":"Enshuang Guo, Lei Li, Jiankun Yang, Yongjian Zhou, Lu Bai, Weiwei Zhu, Qiuyue Hu, Huifen Wang, Hongqiang Liu","doi":"10.1186/s13062-025-00620-3","DOIUrl":"10.1186/s13062-025-00620-3","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is a fatal malignancy that lacking specific therapies. Homeobox B4 (HOXB4) was negatively correlated with poor prognosis in cancers, but its role in hepatocellular carcinoma has not been elucidated.</p><p><strong>Results: </strong>We confirmed that HOXB4 was downregulated in hepatocellular carcinoma tissues and lower HOXB4 expression associated with poor prognosis. Gain- and loss-of function experiments were performed to understand the functional consequences. We revealed that HOXB4 overexpression inhibited proliferation and metastasis of hepatocellular carcinoma cells, accompanied with the decrease in epithelial-mesenchymal transition and increase in cell apoptosis. Database analysis showed that HOXB4 was positively correlated with the immune infiltration. PD-L1 expression was decreased in HOXB4 overexpressed hepatocellular carcinoma cells. HOXB4 overexpression was confirmed to inhibit the progression of hepatocellular carcinoma and promote T cell infiltration in vivo. N6-methyladenosine (m6A) modification was implicated in the tumorigenesis. RNA-seq analysis showed that HOXB4 overexpression modulated METTL7B expression. With the performance of dual-luciferase reporter, ChIP, and DNA pulldown assays, we revealed that HOXB4 binding to METTL7B promoter and inhibited its mRNA expression. The increased aggressiveness of hepatocellular carcinoma cells and the enhanced immune escape, triggered by HOXB4 knockdown, were inhibited via METTL7B downregulation. Methylated RNA immunoprecipitation assay displayed that METTL7B controlled the mRNA decay of TKT in m6A methylation. METTL7B overexpression increase the expression of TKT, ultimately promoting hepatocellular carcinoma progression and immune evasion.</p><p><strong>Conclusions: </strong>HOXB4 mediated the malignant phenotypes and modulated the immune evasion via METTL7B/TKT axis. The HOXB4/METTL7B cascade and its downstream changes might be novel targets for blocking hepatocellular carcinoma progression.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"26"},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566098","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}
Biology DirectPub Date : 2025-03-05DOI: 10.1186/s13062-025-00622-1
Xu Zhang, Fayu Liu, Qigen Fang, Changfu Sun, Jie Fan
{"title":"E3 ligase HERC5-catalyzed UGDH isgylation promotes SNAI1-mediated tumor metastasis and cisplatin resistance in oral squamous cell carcinoma.","authors":"Xu Zhang, Fayu Liu, Qigen Fang, Changfu Sun, Jie Fan","doi":"10.1186/s13062-025-00622-1","DOIUrl":"10.1186/s13062-025-00622-1","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide due to its high aggressive potential and drug resistance. Previous studies have revealed an important function of HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5) in cancer. Six GEO gene microarrays identified HERC5 as a significant upregulated gene in OSCC tissues or cells (log2 Fold change > 1 and adj.p < 0.05). This study aimed to explore the role and underlying mechanisms of HERC5 in OSCC development.</p><p><strong>Results: </strong>High HERC5 expression in OSCC tissues was confirmed by our hospital validation cohort and positively correlated with primary tumor stages. Subsequent functional studies demonstrated that knockdown of HERC5 inhibited the migratory and invasive capabilities with decrease of Vimentin and increase of E-cadherin in OSCC cells. In cisplatin treatment, cell survival rates were significantly reduced in HERC5-silencing OSCC cells, accompanied by the increase in cytotoxicity, DNA damage and apoptosis. OSCC cell-derived tumor xenograft displayed that HERC5 depletion inhibited pulmonary metastasis as well as restored the cisplatin-induced tumor burden. In line with this, overexpression of HERC5 yielded the opposite alterations both in vivo and in vitro. Mechanistically, UDP-glucose 6-dehydrogenase (UGDH) was identified as a HERC5-binding protein. Cysteine residue at position 994 in the HECT domain of HERC5 catalyzed the conjugation of ubiquitin-like protein Interferon-induced 15 kDa protein (ISG15) to UGDH (ISGylation of UGDH) and facilitated its phosphorylation, therefore enhancing SNAI1 mRNA stability. SNAI1 depletion inhibited HERC5 overexpression-triggered invasion and cisplatin resistance of OSCC cells.</p><p><strong>Conclusions: </strong>Our study indicates that HERC5 may be a promising therapeutic target for OSCC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"27"},"PeriodicalIF":5.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566095","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}
Biology DirectPub Date : 2025-02-28DOI: 10.1186/s13062-025-00619-w
Gerry Melino
{"title":"Moving biology direct towards a new dimension.","authors":"Gerry Melino","doi":"10.1186/s13062-025-00619-w","DOIUrl":"10.1186/s13062-025-00619-w","url":null,"abstract":"","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"25"},"PeriodicalIF":5.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530973","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}