bims-exocan 2026-07-12 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2026–07–12
nine papers selected by
Muhammad Rizwan, COMSATS University

Extracellular vesicles derived from cancer-associated fibroblasts facilitate NSCLC progression and metastasis via miR-664b-5p-mediated activation of the CXCL12/CXCR4 chemokine pathway.
Hypoxia-induced exosomal LNCOC1 orchestrates bladder cancer progression via the YBX1/PIK3CA axis and serves as a potential liquid biopsy biomarker.
Extracellular vesicles as systems-level regulators of tumor progression: Integrating signaling networks, microenvironment reprogramming, and therapy resistance.
A Droplet-Microarray Platform for Multiplex Profiling of Breast Cancer Exosome Subtypes in Patients' Blood Plasma Samples.
CAF-derived exosomes inhibit ferroptosis via GALNT14-mediated O-GalNAcylation of SLC7A11 in colorectal cancer.
Optimizing miRNA Loading into Platelet Exosomes via Electroporation: A Comparative Analysis of Buffer Systems and Voltage Parameters for Enhanced Targeted Drug Delivery.
Exosomal transfer of p-AKT drives doxorubicin resistance and predicts poor prognosis in breast cancer.
Identification of exosome-related genes signature based on bioinformatics and machine learning for prognostic prediction in colorectal cancer.
Exosomal B7H3 drives immunosuppression and serves as a biomarker for PD-1 blockage response in head and neck squamous cell carcinoma.

Biochim Biophys Acta Mol Basis Dis. 2026 Jul 09. pii: S0925-4439(26)00223-1. [Epub ahead of print] 168360

Extracellular vesicles derived from cancer-associated fibroblasts facilitate NSCLC progression and metastasis via miR-664b-5p-mediated activation of the CXCL12/CXCR4 chemokine pathway.

Fangping Wang, Defu Li, Yong Li, Bentong Yu, Xin Gan, Yong Wang, Huqiao Luo, Jie Chen, Haiyu Zhou, Quqin Lu, Shiwen Luo.

  Exosomal miRNAs mediate intracellular communication between the tumor microenvironment and cancer cells in non-small cell lung cancer (NSCLC). However, effects of exosomal miRNAs on NSCLC and its mechanisms have not been completely clarified. Here, exosome miRNA profiling and patient serum analysis revealed that the expression level of exosomal miR-664b-5p is significantly elevated in NSCLC, with particularly high levels in cancer-associated fibroblasts (CAFs) and their secreted exosomes. Functionally, miR-664b-5p promotes cell proliferation, migration, and invasion and inhibits apoptosis, thereby promoting malignant progression and metastasis in NSCLC. Moreover, experiments in a CAF-organoid coculture system and a CAF-NSCLC cell coinjection animal model demonstrated that exosomal miR-664b-5p is derived primarily from CAFs and is transferred to NSCLC cells via exosomes, contributing to the malignant phenotype of NSCLC cells, whereas miR-664b-5p knockdown in CAFs attenuated their tumor-promoting ability. Further exploration revealed that G protein γ subunit 11 (GNG11) is a direct functional target gene of miR-664b-5p. GNG11 expression is negatively correlated with miR-664b-5p expression, and ectopic expression of GNG11 partially abrogates the malignant phenotypes induced by miR-664b-5p overexpression in NSCLC. Mechanistically, CAF-derived exosomal miR-664b-5p facilitates NSCLC progression and metastasis by downregulating GNG11, which correlated with activation of the CXCL12/CXCR4 chemokine pathway. Serum exosomal miR-664b-5p levels were positively correlated with tumor burden. Taken together, the results of our study reveal that exosomal miR-664b-5p derived from CAFs can be transferred to NSCLC cells to promote NSCLC progression and metastasis via the CXCL12/CXCR4 axis, supporting the potential of exosomal miR-664b-5p as a biomarker and therapeutic target for NSCLC.

Keywords:  Exosomes; GNG11; Metastasis; NSCLC; miR-664b-5p

DOI:  https://doi.org/10.1016/j.bbadis.2026.168360
Cell Oncol (Dordr). 2026 Jul 07.

Hypoxia-induced exosomal LNCOC1 orchestrates bladder cancer progression via the YBX1/PIK3CA axis and serves as a potential liquid biopsy biomarker.

Haoxiang Xu, Chenglin Yang, Qiangfeng Fu, Shengtao Zeng, Yue Yang, Zhi Cao, Jiahang Wang, Yuansong Xiao, Xiaoming Zhang, Wei Wang.

  Bladder cancer (BCa) is a prevalent genitourinary malignancy characterized by limited specific diagnostic and therapeutic options. Although hypoxia is known to drive tumor progression via exosome-mediated communication, the specific oncogenic roles of hypoxia-induced exosomal long non-coding RNAs (lncRNAs) remain poorly elucidated. Here, we profiled exosomes from normoxic and hypoxic BCa cells using high-throughput sequencing, identifying LNCOC1 as a significantly upregulated lncRNA under hypoxic conditions. Mechanistically, hypoxia-inducible factor 1α (HIF1A) directly binds to the LNCOC1 promoter to drive its transcription and subsequent exosomal encapsulation. Upon transfer to recipient cells, exosomal LNCOC1 promotes BCa cell proliferation, migration, and invasion. It acts as a nuclear scaffold, directly recruiting the transcription factor YBX1 to the PIK3CA promoter, thereby upregulating PIK3CA expression and hyperactivating the PI3K/AKT signaling pathway. Clinically, elevated LNCOC1 levels in tumor tissues and circulating plasma exosomes from 96 BCa patients positively correlated with advanced tumor grade, metastasis, and poor prognosis. Furthermore, circulating exosomal LNCOC1 demonstrated moderate diagnostic efficacy in distinguishing BCa patients from healthy controls (AUC = 0.789) and metastatic from non-metastatic cases (AUC = 0.765). Collectively, these findings elucidate a novel HIF1A/LNCOC1/YBX1/PIK3CA regulatory axis, highlighting circulating exosomal LNCOC1 as a preliminary candidate biomarker for BCa diagnosis that warrants further validation in independent cohorts.

Keywords:  Biomarker; Bladder cancer; Exosomes; Hypoxia; LNCOC1; LncRNA; PIK3CA; Progression; YBX1

DOI:  https://doi.org/10.1007/s13402-026-01257-8
Pathol Res Pract. 2026 Jul 02. pii: S0344-0338(26)00264-5. [Epub ahead of print]286 156611

Extracellular vesicles as systems-level regulators of tumor progression: Integrating signaling networks, microenvironment reprogramming, and therapy resistance.

Deepthi Maria Mathew, Ankit Kumar Bharti S, Anirban Goutam Mukherjee, Abilash Valsala Gopalakrishnan, Babu Gajendran, S Nishu.

  Extracellular vesicles (EVs), once considered cellular debris, are now recognized as critical mediators of intercellular communication that regulate multiple aspects of tumor progression. Rather than acting through isolated pathways, EVs function as system-level regulators integrating intercellular signalling networks, cargo sorting mechanisms and tumor microenvironmental cues to coordinate dynamic and interconnected oncogenic responses. Unlike previous reviews that discuss these processes individually, this review adopts an integrative system-level framework linking EV-mediated oncogenic signaling, microenvironmental remodeling, angiogenesis, premetastatic niche formation, and therapy resistance that can lead to tumor progression. Accumulating evidence highlights EVs as systems-level regulators that integrate oncogenic signaling, microenvironmental remodeling, and adaptive tumor responses. This review presents a mechanistically focused overview of EV biology, moving beyond descriptive aspects of biogenesis to emphasize its functional roles in coordinating cancer progression. EVs facilitate the transfer of bioactive cargo, including proteins, nucleic acids, and lipids, thereby modulating key oncogenic signaling pathways such as PI3K/Akt, Wnt/β-catenin, and TGF-β, which collectively drive proliferation, invasion, and cellular plasticity. In addition, EVs play a pivotal role in reprogramming the tumor microenvironment by promoting angiogenesis, stromal activation, immune modulation, and pre-metastatic niche formation. Emerging evidence further implicates EVs in therapy resistance, where they contribute to drug efflux and the horizontal transfer of resistance-associated molecules. The functional heterogeneity of EV subpopulations and their context-dependent roles are also discussed as key determinants of disease progression. From a translational perspective, EVs are increasingly explored as minimally invasive biomarkers for cancer diagnosis and prognosis, as well as versatile platforms for targeted drug delivery. However, challenges related to isolation techniques, standardization, and clinical scalability remain significant barriers to their implementation. Collectively, this review provides a systems-level perspective on EV-mediated communication networks in cancer, underscoring their dual role as central drivers of tumor progression and promising targets for therapeutic intervention.

Keywords:  Extracellular vesicles; Oncogenic signaling; Therapy resistance; Tumor microenvironment; Tumor progression

DOI:  https://doi.org/10.1016/j.prp.2026.156611
Small. 2026 Jul 06. e13591

A Droplet-Microarray Platform for Multiplex Profiling of Breast Cancer Exosome Subtypes in Patients' Blood Plasma Samples.

Yi Liu, Ruolin Zhang, Jialei Song, Meng Xiao, Yue Meng, Zhiyang Li, Jingyu Shi, Yunyan Tai, Bing Gu, Mo Yang.

  Breast cancer is highly heterogeneous, with distinct subtypes-luminal A, HER2-positive, and triple-negative-each exhibiting unique behaviors and treatment responses. Accurate identification of these subtypes is essential for guiding personalized therapies and improving outcomes. Exosomes, small extracellular vesicles secreted by tumor cells, have emerged as critical biomarkers for cancer diagnostics due to their pivotal role in intercellular communication and their rich molecular cargo reflective of cell origin. However, current exosome-based biosensors struggle to differentiate between breast cancer subtypes, limiting their effectiveness in precision medicine. To address this challenge, we have developed an innovative droplet-microarray platform integrated with a DNase I-assisted MoS2 FRET aptasensor for multiplexed profiling of breast cancer exosome subtypes (luminal A, HER2-positive, and triple-negative). This platform targets three key protein biomarkers-HER2, MUC1, and CD44-leveraging the high specificity of aptamers and the sensitivity of DNase I-assisted signal amplification. Our approach enables high-resolution differentiation of breast tumor exosome profiles with an impressive limit of detection (LOD) of approximately 102 particles/mL. Application of this aptasensor to clinical samples demonstrated excellent predictive accuracy for breast cancer subtype discrimination (luminal A: AUC = 0.95; HER2-positive: AUC = 0.99; triple-negative: AUC = 0.90). By enabling precise identification of breast cancer subtypes, our approach holds promise for enhancing diagnostic accuracy and guiding personalized treatment strategies. This advancement represents a significant step forward in the application of exosome-based diagnostics in precision oncology.

Keywords:  FRET; breast cancer subtypes; exosomes; multiplex detection

DOI:  https://doi.org/10.1002/smll.202513591
Oncogene. 2026 Jul 07.

CAF-derived exosomes inhibit ferroptosis via GALNT14-mediated O-GalNAcylation of SLC7A11 in colorectal cancer.

Jialu Guan, Lingfeng Guo, Shuo Ning, Wenxi Zhao, Tong Wang, Jingjing Wang, Zhen Qi, Jingjing Huang, Jianqi Wang, Yuanfeng Gong, Tiemin Pei, Qinghui Meng, Huayang Pan.

In the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs)-the dominant stromal component-actively shape cancer progression through exosome-mediated communication. Here, we identify hsa_circ_0003892 (circLDLR), a CAF-derived circRNA, as a key factor associated with poor prognosis in colorectal cancer (CRC). During interactions between CAFs and CRC cells, circLDLR is packaged into exosomes and transferred to tumor cells, where it enhances proliferation and metastasis primarily by reducing susceptibility to ferroptosis. Mechanistically, circLDLR stabilizes Polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) by protecting it from ZNRF2-mediated ubiquitination and degradation. This stabilization promotes the O-GalNAcylation of Solute Carrier Family 7 Member 11 (SLC7A11) at Ser26, facilitating its membrane localization and thereby suppressing ferroptosis in CRC cells. Additionally, we demonstrate that the RNA-binding protein EIF4A3 facilitates circLDLR biogenesis within CAFs. Taken together, our study reveals that CAF-derived circLDLR confers ferroptosis resistance and promotes CRC progression via the GALNT14/SLC7A11 axis. Consequently, disrupting exosomal circLDLR transfer between CAFs and CRC cells may offer a promising therapeutic strategy for CRC. Schematic diagram of the mechanism by which CAF-derived circLDLR promotes CRC progression through ferroptosis regulation. In the tumor microenvironment, CAFs highly express circLDLR, whose biogenesis is facilitated by EIF4A3-mediated splicing of LDLR pre-mRNA. circLDLR is then packaged into exosomes and transferred to CRC cells. Within CRC cells, circLDLR specifically binds to GALNT14 and inhibits its ubiquitination and degradation mediated by ZNRF2, thereby enhancing GALNT14 protein stability. Stabilized GALNT14 promotes O-GalNAcylation of SLC7A11 at Ser26, facilitating its membrane localization and increasing cystine uptake. The elevated cystine metabolism enhances GSH production, thereby suppressing ferroptosis and driving CRC cell proliferation and progression.

DOI: https://doi.org/10.1038/s41388-026-03890-x
Mol Biotechnol. 2026 Jul 04.

Optimizing miRNA Loading into Platelet Exosomes via Electroporation: A Comparative Analysis of Buffer Systems and Voltage Parameters for Enhanced Targeted Drug Delivery.

Yuhan Wang, Yali Wang, Qiong Yuan, Zhi Cai, Ling Jiang, Fujiang Xu, Shan Hu.

  Exosomes, which transport miRNAs in vivo, hold significant therapeutic potential for treating diseases. Current methods for loading miRNAs into exosomes include sonication, co-incubation, kit-based transfection, and electroporation, with electroporation being the most efficient and widely used approach. However, standardized protocols for electroporation conditions remain lacking, necessitating the optimization of electroporation parameters to enhance the utility of extracellular vesicles as drug delivery vehicles in vivo. Platelets were isolated from healthy volunteer blood donors, and platelet-derived exosomes were extracted. The exosomes were labeled with specific dyes and loaded with miRNA using Bio-Rad Gene Pulser Electroporation buffer or 50 mM trehalose. Electroporation was performed at 150 V, 350 V, and 500 V. The miRNA-loaded exosomes were then co-incubated with cells. The efficiency of miRNA delivery was evaluated through fluorescence co-localization, nanoparticle tracking analysis, and qPCR. Our findings demonstrate that the Bio-Rad Gene Pulser Electroporation buffer is highly effective as an electroporation medium for exosomes. Optimal miRNA transfection efficiency and cellular uptake were achieved at 350 V, with significantly higher exosome internalization observed under these conditions. Utilizing the Bio-Rad Gene Pulser Electroporation buffer at 350 V enhances both miRNA loading efficiency into extracellular vesicles and subsequent cellular uptake. This study establishes an optimized electroporation protocol, addressing limitations in existing methodologies and advancing the potential of extracellular vesicles as a robust platform for miRNA-based therapeutic delivery.

Keywords:  Electroporation; Exosomes; MicroRNA; Platelet; Trehalose; Voltage

DOI:  https://doi.org/10.1007/s12033-026-01590-1
Mol Biol Rep. 2026 Jul 08. pii: 1121. [Epub ahead of print]53(1):

Exosomal transfer of p-AKT drives doxorubicin resistance and predicts poor prognosis in breast cancer.

Shazia Gul, Jasmeena Jan, Rumaisa Mohidin, Owais Mohmad Bhat, Abid Hamid Dar, Mohammad Afzal Zargar, Nissar Ahmad Wani.

   BACKGROUND: Breast cancer remains the second leading cause of cancer-related mortality among women worldwide. Doxorubicin is widely used in breast cancer therapy, however, its clinical efficacy is frequently compromised by the development of drug resistance. Growing evidence suggests that small extracellular vesicles/exosomes are involved in intercellular communication might play a critical role in the horizontal transfer of chemoresistance. In this study, we investigated the contribution of exosomes to the acquisition and propagation of doxorubicin resistance in breast cancer.
METHODS: Cell viability, proliferation and colony formation was evaluated using MTT and crystal violet staining. Exosomes were isolated and comprehensively characterized by Scanning electron microscopy (SEM), Dynamic light scattering (DLS) and Western blotting. Activation of different signalling molecules was assessed by using phosphokinase array and Western blotting. Expression and pathway analysis of different signalling molecules in breast cancer patients was done using online patient datasets and bioinformatic analysis.
RESULTS AND CONCLUSION: Doxorubicin resistant cells exhibited enhanced cellular proliferation, glucose uptake and increased lactate production. Exosomes of DOX-resistant cells significantly enhanced cell proliferation of DOX-sensitive breast cancer cells and reduced the sensitivity of DOX-sensitive breast cancer cells to doxorubicin. Delineation of molecular mechanisms revealed dysregulation in cellular signals responsible for imparting doxorubicin resistance in doxorubicin sensitive breast cancer cells. Among different cellular signals, AKT and STAT3 emerged as key hub proteins, with phosphorylated AKT playing a dominant role in mediating doxorubicin resistance. Clinical data further supported the association between activated AKT signalling and poor therapeutic response. Importantly, pharmacological inhibition of AKT effectively re-sensitized doxorubicin resistant breast cancer cells to doxorubicin. Collectively, these findings identify exosomal phosphorylated AKT as a critical mediator of doxorubicin resistance and a potential therapeutic target in breast cancer patient's resistant to doxorubicin.

Keywords:  AKT; Breast cancer; Doxorubicin; Drug combination.; Exosomes; Resistance

DOI:  https://doi.org/10.1007/s11033-026-12306-8
Discov Oncol. 2026 Jul 04.

Identification of exosome-related genes signature based on bioinformatics and machine learning for prognostic prediction in colorectal cancer.

Kaisong Wang, Tingyu Chen, Yiqiang Chen, Jiajing Zhao, Ruizhi Fu, Xiaoling Xu, Genghong Su, Shubiao Chen.

   BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant tumor with increasing incidence and mortality rates worldwide. Exosomes are secretory vesicles generated by the endosomal system within cells. Previous studies have reported that exosome-related genes (ERGs) are associated with the progression of malignancies. This study investigates the role of ERGs in CRC, evaluates their impact on CRC prognosis, and explores inter-individual differences among CRC patients in different risk groups.
METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) algorithm was employed to identify ERGs associated with CRC. Subsequently, various bioinformatics approaches, including enrichment analysis, consensus clustering, and survival analysis, were utilized to investigate the role of ERGs in individual CRC patients. Furthermore, exosome-related signature genes were refined using the Random Forest (RF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms based on colon cancer samples from The Cancer Genome Atlas (TCGA) database. An ERG-related gene signature was then constructed to calculate the ERG-associated risk score for each patient, which was validated using data from the Gene Expression Omnibus (GEO) database. Based on the risk scores, we assessed the responsiveness of different CRC individuals to immunotherapy and chemotherapy. Finally, single-cell analysis provided deeper insights into the relationship between ERGs and CRC, and a nomogram was established to enhance their clinical utility.
RESULTS: This study identified two ERG-related subtypes that exhibited significant differences in prognosis, enriched pathways, clinicopathological features, and immune characteristics. Moreover, CRC individuals with high ERG-related risk scores were associated with poor responsiveness to immunotherapy and increased sensitivity to various chemotherapeutic agents. Single-cell analysis revealed that ERGs were highly expressed in monocytes. The model developed in this study demonstrated strong predictive accuracy for assessing ERG-related risk in CRC patients.
CONCLUSIONS: This study identified two hub genes, CUL4A and UCHL1, highlighting the diagnostic and prognostic significance of ERGs in CRC and offering new insights into CRC treatment. Additionally, the ERG signature plays a crucial role in predicting individualized prognosis and facilitating the development of novel therapeutic strategies for CRC patients. Nevertheless, further studies are necessary to bring statistically derived risk models into clinically applicable assays.

Keywords:  Bioinformatics; Colorectal cancer; Exosome-related genes; Prediction; Prognosis

DOI:  https://doi.org/10.1007/s12672-026-05522-y
Cancer Biol Med. 2026 Jul 03. pii: j.issn.2095-3941.2025.0835. [Epub ahead of print]

Exosomal B7H3 drives immunosuppression and serves as a biomarker for PD-1 blockage response in head and neck squamous cell carcinoma.

Wen Wang, Chulong Xie, Juncong Luo, Leru Kuang, Yihong Wu, Nini Li, Xiaoli Liu, Xiaoyu Feng, Zizi Li, Zhanyu Li, Hongyu Zhang, Jiaoping Mi, Qi Zeng.

   OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) display a remarkably low response rate to immune checkpoint inhibitor (ICI) therapy. Currently, there is an urgent unmet need for reliable non-invasive biomarkers capable of predicting clinical therapeutic outcomes. This study sought to elucidate the role of exosomal B7H3 in the HNSCC immune microenvironment and evaluate the potential utility of B7H3 as a predictive biomarker for ICI therapy.
METHODS: Exosomal B7H3 was characterized via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The biological functions and regulatory mechanisms underlying exosomal B7H3 were explored using Western blot, ELISA, flow cytometry, and immunofluorescence staining. In vivo animal studies and immunohistochemical (IHC) analyses of clinical tissue specimens were further performed to verify the in vitro findings.
RESULTS: In the present study secretion of exosomal B7H3 was significantly elevated in HNSCC. Functional assays confirmed that HNSCC-derived exosomal B7H3 mediates robust immunosuppression both in vitro and in vivo. Notably, HNSCC cells exhibited a mutually exclusive pattern of B7H3 and PD-L1 expression. Specifically, high B7H3 expression was closely associated with resistance to anti-PD-1 therapy. A significant negative correlation was detected between circulating exosomal B7H3 and exosomal PD-L1 levels. Furthermore, HNSCC patients with high circulating exosomal B7H3 levels exhibited poorer responses to anti-PD-1 treatment compared to HNSCC patients with low exosomal B7H3 expression.
CONCLUSIONS: The findings herein demonstrated that exosomal B7H3 exerts potent immunosuppressive effects and displays a mutually exclusive expression pattern with PD-L1, thereby contributing to anti-PD-1 immunotherapy resistance in HNSCC. These results provide a solid theoretical basis for using exosomal B7H3 as a non-invasive predictive biomarker and highlight a promising novel therapeutic target for HNSCC patients.

Keywords:  B7H3; HNSCC; PD-1; exosomes; immunotherapy

DOI:  https://doi.org/10.20892/j.issn.2095-3941.2025.0835