TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.100638
Blanca Cómitre-Mariano, Berta Segura-Collar, Gabriel Vellila-Alonso, Rubén Contreras, Aurelio Henandez-Lain, Manuel Valiente, Juan M Sepulveda, Stephen Garrett Marcus, Guillermo García-Posadas, Luis Jiménez-Roldán, Ángel Perez-Nuñez, Ricardo Gargini
{"title":"S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture.","authors":"Blanca Cómitre-Mariano, Berta Segura-Collar, Gabriel Vellila-Alonso, Rubén Contreras, Aurelio Henandez-Lain, Manuel Valiente, Juan M Sepulveda, Stephen Garrett Marcus, Guillermo García-Posadas, Luis Jiménez-Roldán, Ángel Perez-Nuñez, Ricardo Gargini","doi":"10.7150/thno.100638","DOIUrl":"10.7150/thno.100638","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma IDH wild type (GBM IDH wt) has a poor prognosis and a strongly associated with inflammatory processes. Inflammatory molecules generate positive feedback with tumor cells fueling tumor growth as well as recruitment of immune cells that promote aggressiveness. Although the role of many inflammatory molecules is well known, there are many macromolecules, such as the S100A proteins, whose role is only now beginning to be established. <b>Methods:</b> Using RNA-seq, bioinformatics tools and a cohort of glioma patients to validate the results, we have analysed the inflammatory processes involved in glioma. Transcriptional profiles were also used to define biological processes of relevance to specific S100A proteins. Finally, we characterized the relevant immune populations with an IHC analysis and transcriptional profiling. <b>Results:</b> We have noted an increased expression of S100A in GBM IDH wt compared to gliomas IDH mutants. This allowed us to analyse the involvement of different members of the family, such as S100A9, A11 and A13 as possible regulators of inflammatory processes in the GBM-IDH wt microenvironment. Thus, we observed that S100A9 is located in hypoxic areas linked to the function of neutrophils, S100A11 is found in vascular areas associated with the function of perivascular pericytes and macrophages, and finally, S100A13 which is related to the dysfunction of microglia. <b>Conclusion:</b> Our findings define different functions for S100A9, A11 and A13 proteins that are associated with the architecture of the glioblastoma microenvironment and define its progression. Moreover, these alterations can be reversed by the RAGE inhibitor, Azeliragon which is in a phase I/II clinical trial NCT05635734.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 2","pages":"726-744"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.104190
Yubing Zhang, Jiaqi Xing, Juan Jiang, Maoliang Liao, Guojun Pan, Yanfeng Wang
{"title":"Hypoxia-responsive nanoparticles for fluorescence diagnosis and therapy of cancer.","authors":"Yubing Zhang, Jiaqi Xing, Juan Jiang, Maoliang Liao, Guojun Pan, Yanfeng Wang","doi":"10.7150/thno.104190","DOIUrl":"10.7150/thno.104190","url":null,"abstract":"<p><p>Hypoxia, caused by rapid tumor growth and insufficient oxygen supply, is a defining characteristic of numerous solid tumors and exerts a significant influence on tumor growth, metastasis, and invasion. Early diagnosis and effective killing of tumor cells are crucial for cancer treatment. In recent years, the emergence of nanomaterials has overcome the difficulties in the delivery of chemotherapeutic drugs and contrast agents to tumor area. In this review, we summarize the development of hypoxia-responsive nanoparticles for fluorescence imaging and tumor therapy in the last five years, and further discuss their design strategies and applications in bioimaging. In addition, we discuss the therapeutic strategies of hypoxia-responsive prodrugs on different nanoplatforms and the future prospects of hypoxia-responsive nanomedicine in tumor therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1353-1375"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JARID1D-dependent androgen receptor and JunD signaling activation of osteoclast differentiation inhibits prostate cancer bone metastasis through demethylating H3K4.","authors":"Yaohua Hu, Zhite Zhao, Qinghua Xie, Hui Li, Chenyang Zhang, Xinglin He, Yifan Ma, Caiqin Zhang, Qinlong Li, Changhong Shi","doi":"10.7150/thno.104135","DOIUrl":"10.7150/thno.104135","url":null,"abstract":"<p><p><b>Rationale:</b> Bone metastasis and skeletal-related complications are primary causes of mortality in advanced-stage prostate cancer (PCa). Epigenetic regulation, particularly histone modification, plays a key role in this process; however, the underlying mechanisms remain elusive. <b>Methods and Results:</b> In mouse models, JARID1D was an important mediator of both visceral and bone metastases. Chromatin immunoprecipitation (ChIP) and immunofluorescence (IF) techniques showed that the H3K4me3 demethylation activity of JARID1D is a key factor in the dynamic regulation of androgen receptor (AR) expression. Further analysis using western blotting and bone culture systems indicated that knocking down JARID1D enhanced the expression of monoamine oxidase A (MAOA) through the AR signaling pathway, leading to increased secretion of the nuclear factor kappa B (NF-κB) ligand receptor activator (RANKL) by PCa cells. This in turn promotes osteoclast differentiation and facilitates bone metastasis. In addition, single-cell sequencing results indicated that a reduction in JARID1D levels directly affected osteoclasts, stimulated JunD transcription, and accelerated PCa bone metastasis progression. Finally, both <i>in vivo</i> and <i>in vitro</i> experiments confirmed that the JARID1D agonist JIB-04 effectively blocked these molecular pathways, thereby delaying the onset of bone metastasis in PCa. <b>Conclusions:</b> These insights provide a theoretical foundation for targeting JARID1D and related molecules in the treatment of PCa bone metastasis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1320-1337"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.103266
Ke Yan, Qinghe Zhang, Qiuping Liu, Yi Han, Zuguo Liu
{"title":"Advances in adhesive hydrogels applied for ophthalmology: An overview focused on the treatment.","authors":"Ke Yan, Qinghe Zhang, Qiuping Liu, Yi Han, Zuguo Liu","doi":"10.7150/thno.103266","DOIUrl":"10.7150/thno.103266","url":null,"abstract":"<p><p>Adhesive hydrogels, composed of hydrophilic polymers arranged in a three-dimensional network, have emerged as a pivotal innovation in ophthalmology due to their ability to securely adhere to ocular tissues while providing sustained therapeutic effects. The eye, with its delicate structure and specific needs, presents unique challenges for drug delivery and tissue regeneration. This review explores the transformative potential of adhesive hydrogels in addressing these challenges across a range of ocular conditions, including corneal injuries, cataracts, glaucoma, vitreoretinal disorders, and ocular trauma. By detailing the mechanisms of polymerization and adhesion, this paper highlights how these materials can be customized for specific ophthalmic applications, offering insights into their current use and future possibilities. The emphasis is placed on the clinical significance and future directions of adhesive hydrogels in advancing ophthalmic therapy, potentially revolutionizing the treatment of complex eye diseases.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"915-942"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.104872
Jieyu Liu, Xiaoling Li, Yinggang Li, Qiyong Gong, Kui Luo
{"title":"Metformin-based nanomedicines for reprogramming tumor immune microenvironment.","authors":"Jieyu Liu, Xiaoling Li, Yinggang Li, Qiyong Gong, Kui Luo","doi":"10.7150/thno.104872","DOIUrl":"10.7150/thno.104872","url":null,"abstract":"<p><p>Immunotherapy has transformed current cancer management, and it has achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing the activity of immune cells and facilitating tumor immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator of cellular energy metabolism and homeostasis, has gained growing attention in anti-tumor immunity. Metformin is usually considered as a cornerstone in diabetes management, and its role in activating the AMPK pathway has also been extensively explored in cancer therapy although the findings on its role remain inconsistent. Metformin in a nanomedicine formulation has been found to hold potential in reprogramming the immunosuppressive TME through immunometabolic modulation of both tumor and immune cells. This review elaborates the foundation and progress of immunometabolic reprogramming of the TME via metformin-based nanomedicines, offering valuable insights for the next generation of cancer therapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"993-1016"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Bisphosphonate-mineralized nano-IFNγ suppresses residual tumor growth caused by incomplete radiofrequency ablation through metabolically remodeling tumor-associated macrophages.","authors":"Zhicheng Yan, Bing Wang, Yuhan Shen, Junji Ren, Meifang Chen, Yunhui Jiang, Hao Wu, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang, Wei Yang, Bing He","doi":"10.7150/thno.100998","DOIUrl":"https://doi.org/10.7150/thno.100998","url":null,"abstract":"<p><p><b>Rationale:</b> Radiofrequency ablation (RFA), as a minimally invasive surgery strategy based on local thermal-killing effect, is widely used in the clinical treatment of multiple solid tumors. Nevertheless, RFA cannot achieve the complete elimination of tumor lesions with larger burden or proximity to blood vessels. Incomplete RFA (iRFA) has even been validated to promote residual tumor growth due to the suppressive tumor immune microenvironment (TIME). Therefore, exploring strategies to remodel TIME is a key issue for the development of RFA therapy. <b>Methods:</b> The negative effect of iRFA on colorectal cancer therapy was firstly investigated. Then a zoledronate-mineralized nanoparticle loaded with IFNγ (Nano-IFNγ/Zole) was designed and its tumor suppressive efficacy was evaluated. Finally, the metabolic reprogramming mechanism of Nano-IFNγ/Zole on tumor-associated macrophages (TAMs) was studied in detail. <b>Results:</b> We found iRFA dynamically altered TIME and promoted TAM differentiation from M1 to M2. Nano-IFNγ/Zole was fabricated to metabolically remodel TAMs. IFNγ in Nano-IFNγ/Zole concentrated in the ablation site to play a long-term remodeling role. Acting on mevalonate pathway, Nano-IFNγ/Zole was discovered to reduce lysosomal acidification and activate transcription factor TFEB by inhibiting isoprene modification of the Rab protein family. These mechanisms, in conjunction with IFNγ-activated JAK/STAT1 signaling, accelerated the reprogramming of TAMs from M2 to M1, and suppressed tumor recurrence after iRFA. <b>Conclusions:</b> This study elaborates the synergistic mechanism of zoledronate and IFNγ in Nano-IFNγ/Zole to reshape suppressive TIME caused by iRFA by remodeling TAMs, and highlights the important value of metabolically induced cellular reprogramming. Since both zoledronate and IFNγ have already been approved in clinics, this integrative nano-drug delivery system establishes an effective strategy with great translational promise to overcome the poor prognosis after clinically incomplete RFA.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 3","pages":"1057-1076"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.103376
Mingxia Jiang, Huapan Fang, Huayu Tian
{"title":"Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer.","authors":"Mingxia Jiang, Huapan Fang, Huayu Tian","doi":"10.7150/thno.103376","DOIUrl":"10.7150/thno.103376","url":null,"abstract":"<p><p>The metabolism of cancer and immune cells plays a crucial role in the initiation, progression, and metastasis of cancer. Cancer cells often undergo metabolic reprogramming to sustain their rapid growth and proliferation, along with meeting their energy demands and biosynthetic needs. Nevertheless, immune cells execute their immune response functions through the specific metabolic pathways, either to recognize, attack, and eliminate cancer cells or to promote the growth or metastasis of cancer cells. The alteration of cancer niches will impact the metabolism of both cancer and immune cells, modulating the survival and proliferation of cancer cells, and the activation and efficacy of immune cells. This review systematically describes the key characteristics of cancer cell metabolism and elucidates how such metabolic traits influence the metabolic behavior of immune cells. Moreover, this article also highlights the crucial role of immune cell metabolism in anti-tumor immune responses, particularly in priming T cell activation and function. By comprehensively exploring the metabolic crosstalk between cancer and immune cells in cancer niche, the aim is to discover novel strategies of cancer immunotherapy and provide effective guidance for clinical research in cancer treatment. In addition, the review also discusses current challenges such as the inadequacy of relevant diagnostic technologies and the issue of multidrug resistance, and proposes potential solutions including bolstering foundational cancer research, fostering technological innovation, and implementing precision medicine approaches. In-depth research into the metabolic effects of cancer niches can improve cancer treatment outcomes, prolong patients' survival period and enhance their quality of life.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 1","pages":"155-188"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optical coherence tomography (OCT) and OCT angiography: Technological development and applications in brain science.","authors":"Luyao Yang, Pengyu Chen, Xiaofei Wen, Qingliang Zhao","doi":"10.7150/thno.97192","DOIUrl":"10.7150/thno.97192","url":null,"abstract":"<p><p>Brain diseases are a leading cause of disability and death worldwide. Early detection can lead to earlier intervention and better outcomes for patients. In recent years, optical coherence tomography (OCT) and OCT angiography (OCTA) imaging have been widely used in stroke, traumatic brain injury (TBI), and brain cancer due to their advantages of <i>in vivo</i>, unlabeled, and high-resolution 3D microvessel imaging at the capillary resolution level. This review summarizes recent advances and challenges in living brain imaging using OCT/OCTA, including technique modality, types of diseases, and theoretical approach. Although there may still be many limitations, with the development of lasers and the advances in artificial intelligence are expected to enable accurate detection of deep cerebral hemodynamics and guide intraoperative tumor resection <i>in vivo</i> in the future.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 1","pages":"122-140"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.100897
Sylvain Bodard, Louise Denis, Georges Chabouh, Dany Anglicheau, Olivier Hélénon, Jean-Michel Correas, Olivier Couture
{"title":"First clinical utility of sensing Ultrasound Localization Microscopy (sULM): identifying renal pseudotumors.","authors":"Sylvain Bodard, Louise Denis, Georges Chabouh, Dany Anglicheau, Olivier Hélénon, Jean-Michel Correas, Olivier Couture","doi":"10.7150/thno.100897","DOIUrl":"10.7150/thno.100897","url":null,"abstract":"<p><p><b>Rationale:</b> Renal pseudotumors, which mimic tumors on imaging, pose diagnostic challenges that can lead to unnecessary interventions. Sensing ultrasound localization microscopy (sULM) is an advanced imaging technique that uses ultrasound imaging and microbubbles as sensors to visualize kidney functional units. This study aims to investigate whether sULM could differentiate between renal pseudotumors and tumors based on the presence of glomeruli. <b>Methods:</b> Eleven patients (6 tumors, 6 pseudotumors - 1 patient with 2 pseudotumors) were included. Data on patient demographics, tumor characteristics, and sULM metrics were collected. Glomeruli were quantified and compared among tumors, pseudotumors, and renal cortex using sULM. Additional metrics, i.e., normalized speed and dispersity, were also analyzed. <b>Results:</b> Renal tumors exhibited fewer detected glomeruli paths (mean: 10 ± 6 /cm<sup>2</sup> [range: 4-20]) compared to pseudotumors (26 ± 5 /cm<sup>2</sup> [19-32], p < 0.001) and normal renal cortex (26 ± 6 /cm<sup>2</sup> [15-35], p < 0.01). Tumors displayed lower dispersity (0.13 ± 0.06 arbitrary units [a.u.] [0.07-0.20]) than both the renal cortex (0.3 ± 0.1 a.u. [0.1-0.4], p = 0.0012) and pseudotumors (0.22 ± 0.05 a.u. [0.16-0.25], p = 0.0389), and lower normalized speeds of 0.08 ± 0.04 without units (w.u.) [range: 0.03-0.17] compared to the renal cortex (0.18 ± 0.07 w.u. [0.11-0.28], p = 0.0014) and pseudotumors (0.14 ± 0.02 w.u. [0.12-0.16], p = 0.0497). sULM could effectively differentiate renal pseudotumors from tumors based on glomerular detection and metrics estimation. <b>Conclusion:</b> This initial exploration into the clinical utility of sULM suggests it could provide a noninvasive tool to support patient management, particularly for individuals with contraindications to conventional imaging methods. Further studies are needed to confirm these preliminary findings.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 1","pages":"233-244"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TheranosticsPub Date : 2025-01-01DOI: 10.7150/thno.102391
Hou-Fu Xia, Xiao-Le Wang, He-Jing Zhang, Kui-Ming Wang, Lin-Zhou Zhang, Yang Yang, Xin Shi, Gang Chen
{"title":"PCBP2-dependent secretion of miRNAs via extracellular vesicles contributes to the EGFR-driven angiogenesis.","authors":"Hou-Fu Xia, Xiao-Le Wang, He-Jing Zhang, Kui-Ming Wang, Lin-Zhou Zhang, Yang Yang, Xin Shi, Gang Chen","doi":"10.7150/thno.102391","DOIUrl":"https://doi.org/10.7150/thno.102391","url":null,"abstract":"<p><p><b>Rationale:</b> The EGFR-driven angiogenesis is crucial in solid tumors, particularly through the delivery of biomolecules via extracellular vesicles (EVs), but the mechanism by which EGFR regulates EV cargo is still unclear. <b>Methods:</b> First, cell co-culture and murine tumor models were employed to examine the impact of EGFR overexpression on the pro-angiogenic properties of small EVs (sEVs) derived from oral squamous cell carcinoma (OSCC). Small RNA sequencing was then used to compare the miRNA profiles of OSCC-sEVs with and without EGFR overexpression, followed by functional enrichment and motif analyses of the differentially expressed miRNAs. Next, miRNA pull-down assays were conducted to identify potential molecules involved in sorting these miRNAs. Finally, the role of the candidate sorting protein was validated using existing public database, tissue samples, cell lines, and murine tumor models. <b>Results:</b> EGFR overexpression significantly enhances the pro-angiogenic effects of OSCC-sEVs, accompanied by a marked increase in the content of nucleic acid cargo carried in these sEVs. Small-RNA sequencing identified a group of miRNAs that were significantly enriched in OSCC-sEVs due to EGFR overexpression, which primarily functioned in angiogenesis and shared a characteristic \"GGGU\" motif. EGFR overexpression also strengthened the binding of PCBP2 with miRNAs containing this \"GGGU\" motif, thereby promoting their secretion through sEVs to support tumor angiogenesis. Mechanismly, EGFR overexpression upregulates PCBP2 protein content by activating its transcription rather than regulating the mRNA stability in OSCC cells. Additionally, depletion of PCBP2 impaired the EGFR-driven tumor angiogenesis by inhibiting the secretion of pro-angiogenic miRNAs through sEVs. <b>Conclusions:</b> EGFR boosts PCBP2 expression via transcriptional regulation, which then promotes the loading of specific miRNAs into sEVs by binding to the \"GGGU\" motif, thereby driving tumor angiogenesis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 4","pages":"1255-1271"},"PeriodicalIF":12.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}