bims-exocan 2025-07-20 papers

Issue of 2025–07–20
five papers selected by
Muhammad Rizwan, COMSATS University

Curr Cancer Drug Targets. 2025 Jul 11.

CD133+-Derived Exosomes Carrying EIF3B Mediate Cell Metastasis and Stemness in Colorectal Cancer.

Xiangwei Liao, Xiaodong Han, Yu Wang, Jun Yan, Zhenqian Wu.

BACKGROUND: Colorectal cancer (CRC) is among the most widespread malignancies worldwide and is a leading cause for cancer mortality. The interstitial interaction between cancer and stem cells is important during cancer cell metastasis.
OBJECTIVE: In this study, we aimed to elucidate the regulatory role and the underlying mechanisms controlling the activity of exosomes derived from cancer stem cells (CSCs).
METHODS: Our group isolated exosomes from CSCs and non-CSCs to examine their regulatory mechanisms using Transwell migration, Cell Counting Kit-8 (CCK-8), and 5-ethynyl-2'-deoxyuridine (EdU) assays.
RESULTS: The role of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in CRC was examined using an in vivo tumorigenesis mouse model. It was found that treatment with exosomes isolated from CD133+ cells (CD133+Exos) promoted the proliferation and migration of SW480 cells. The downregulation of EIF3B reduced the proliferation and migration-promoting effects of CD133+ Exos on SW480 cells. Furthermore, CD133+ Exos treatment promoted the tumorigenesis of SW480 cells.
CONCLUSION: Our findings demonstrate that CSC-derived exosomes transport EIF3B into CRC cells to initiate epithelial-to-mesenchymal transition (EMT) and promote metastasis.

Keywords: CD133<sup>+</sup>; EIF3B; Exosomes; colorectal cancer; digestive system.; intestinal neoplasms

DOI: https://doi.org/10.2174/0115680096346009250628215410

Front Oncol. 2025 ;15 1593827

Tumor-derived exosomal lncRNA SNHG4 promotes triple-negative breast cancer progression by targeting XPO5.

Zhi-Wen Wang, Hou-Sheng Yang, Hong-Shan Guo, Yue-Ying Li, Jin-Yun Zhong, Shu Jiang, Jia-Peng Li, Zhong-Yi Yang, Chuan-Yi Zhou, Jun Wang, Xing-Hua Liao, Lei Mao.

Background: Triple-negative breast cancer (TNBC) is the subtype of advanced breast cancer with the shortest survival time and the poorest prognosis, and treatment options are relatively limited. Exosomes, small extracellular vesicles enriched with bioactive molecules, are critical mediators of intercellular communication and have been implicated in cancer progression. The aim of this study was to investigate the molecular mechanism of exosomes promoting the proliferation and migration of TNBC.
Methods: In this study, exosomes were identified by Flow cytometry and transmission electron microscopy, and RNA sequencing (RNA-seq) was used to identify differentially expressed genes and downstream regulatory molecules in exosomes. RNA-seq results were supported by bioinformatics analysis and Western blot analysis. Functional assays including in vivo tumor formation, Colony formation Assay, Scratch migration and transwell assays were performed to study exosomes related phenomena and mechanism.
Results: Serum-derived exosomes from patients with TNBC can induce TNBC progression in vitro and in vivo. lncRNA SNHG4 was most significantly up-regulated in exosomes, and overexpression of lncRNA SNHG4 significantly promoted the proliferation and migration of TNBC cells. In addition, lncRNA SNHG4 promotes TNBC cell proliferation and migration by upregulating the expression of Exportin 5(XPO5). Silencing XPO5 can effectively attenuate the tumor-promoting effect of serum exosomes in TNBC patients. Mechanistically, lncRNA SNHG4 acts through XPO5-mediated pathways. Silencing XPO5 can effectively inhibit the tumor-promoting effect mediated by lncRNA SNHG4.
Conclusions: Taken together, our study revealed that the exosome lncRNA SNHG4 exerts its oncogenic role by activating XPO5-mediated pathways, thereby regulating TNBC cell proliferation and migration. This can be considered as a potential target for TNBC molecular therapy.

Keywords: TNBC; XPO5; exosome; lncRNA SNHG4; migration; proliferation

DOI: https://doi.org/10.3389/fonc.2025.1593827

DNA Cell Biol. 2025 Jul 14.

Exosome-Mediated circRNA Hsa_Circ_0113050 Enhances Colorectal Cancer Cell Malignancy by Interacting with EIF4A3.

Yuan Tian, Chen He.

The exosome-mediated circular RNAs (circRNAs) play a crucial role in tumorigenesis. The present study investigated the role of the exosome-mediated circRNA hsa_circ_0113050 in colorectal cancer (CRC) through its interaction with the eukaryotic translation initiation factor 4A3 (EIF4A3). CRC-derived exosomes were isolated and characterized by differential ultracentrifugation, transmission electron microscopy, and nanoparticle tracking analysis. The hsa_circ_0113050 expressions in CRC and exosomes were confirmed through a bioinformatic analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Cell functional and in vivo assays were applied to evaluate the effects of exosomes and hsa_circ_0113050 on CRC cell malignancy. The interaction between EIF4A3 and hsa_circ_0113050 was analyzed by RNA immunoprecipitation, Western blotting, and qRT-PCR assays. CRC-derived exosomes with diameters of 102 and 104 nm enhanced the ability of CRC cells to proliferate, migrate, and invade. hsa_circ_0113050 was highly expressed in CRC tissues and CRC-derived exosomes. Silencing hsa_circ_0113050 in exosomes effectively reversed the exosome-induced CRC cell malignancy. Furthermore, EIF4A3 bound to the linear gene (EIF3I) of hsa_circ_0113050 to enhance the hsa_circ_0113050 expression in the CRC cells. In conclusion, the present study is the first to reveal that exosome-mediated hsa_circ_0113050 enhances CRC cell malignancy by interacting with EIF4A3. Our study findings provide new mechanistic insights into circRNA regulation and highlight a potential therapeutic target for CRC.

Keywords: EIF4A3; circRNA; colorectal cancer; exosomes; hsa_circ_0113050

DOI: https://doi.org/10.1177/10445498251359374

Cell Mol Immunol. 2025 Jul 14.

The role of exosomes in immunopathology and potential therapeutic implications.

Wenhui Wang, Shuya Qiao, Xianghui Kong, Gensheng Zhang, Zhijian Cai.

Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, are released by various cells. Among these subtypes, exosomes have been extensively studied and demonstrated to be crucial mediators of intercellular communication involving multiple physiological and pathological processes. Four primary steps influence the biogenesis of exosomes: generation of early endosomes, formation and maturation of multivesicular bodies (MVBs), MVB and plasma membrane fusion for exosome release, and MVB fusion with lysosomes for degradation. During the formation and maturation of MVBs, the main effector molecules, such as RNAs and proteins, are sorted into exosomes via diverse mechanisms. However, the effector molecules of exosomes are dynamic and reflect cell states in real time. Therefore, exosomes secreted by cells under disease conditions are often pathogenic. This review focuses on recent advances in the understanding of exosome biogenesis and the immunopathological effects of exosomes. In addition, potential strategies to mitigate the pathological effects of exosomes are summarized in this review.

Keywords: Biogenesis; Cargo sorting; EVs; Exosomes; Immunopathology; Tumor

DOI: https://doi.org/10.1038/s41423-025-01323-5

Front Immunol. 2025 ;16 1603855

Exosomal PD-L1 detection in cancer predictive biomarker for response to immune checkpoint blockade therapy.

Tetsuichi Kansha, Xiaojuan Ma, Hao Wang, Xiaotong Yu, Ying Song, Zhengyang Guo, Jiagui Song, Lixiang Xue, Jianling Yang.

Programmed death-ligand 1 (PD-L1) carried by tumor-derived exosomes has emerged as a critical mediator of immune evasion and resistance to immune checkpoint blockade therapy. Unlike membrane-bound PD-L1, exosomal PD-L1 is systemically distributed and capable of suppressing T cell activity at distant sites. This review summarizes the current understanding of exosomal PD-L1 biogenesis, its immunosuppressive mechanisms, and its clinical relevance across multiple cancer types. We highlight its potential as a non-invasive biomarker for predicting therapeutic response and monitoring disease progression. Compared with tissue-based PD-L1 assessment, exosomal PD-L1 offers advantages in accessibility and dynamic reflection of tumor immune status. However, challenges remain regarding standardization of detection methods and clinical interpretation. Future directions include the integration of exosomal PD-L1 profiling into immunotherapy decision-making and the development of therapeutic strategies targeting exosome secretion. These insights may contribute to overcoming resistance in immunologically inert tumors and advancing precision oncology.

Keywords: cancer biomarkers; early detection; exosomal PD-L1; immune checkpoint blockade; liquid biopsy

DOI: https://doi.org/10.3389/fimmu.2025.1603855