bims-exocan 2025-09-21 papers

Issue of 2025–09–21
four papers selected by
Muhammad Rizwan, COMSATS University

Transl Cancer Res. 2025 Aug 31. 14(8): 5012-5027

The functional role of exosomal miRNA-675-3p derived from patients with hepatocellular carcinoma.

Chi Liang, Xiang Ji, Shan Liu, Liancheng Xu, Yicheng Xiong, Guanyi Cao.

Background: Hepatocellular carcinoma (HCC) is one of the most common solid tumors, resulting in poor survival and high mortality worldwide. MicroRNAs (miRNAs) contained in serum exosomes are being increasing used as targets for disease diagnosis and treatment. However, the role and the diagnostic potential of exosome-transported miRNAs in HCC remain largely underexplored. Therefore, this study aims to identify differentially expressed exosomal miRNAs in the serum of HCC patients and healthy individuals, clarify the biological function of the key miRNAs in HCC progression, and explore its potential as a diagnostic and therapeutic biomarker for HCC.
Methods: In this study, the serum-derived exosomes of patients with HCC and healthy individuals were characterized via transmission electron microscopy (TEM), Western blot assay, and nanoparticle tracking analysis (NTA). The serum-derived exosomes were labeled with PKH-67, and the transport to recipient HCC cells was observed with confocal microscopy. Differentially expressed miRNAs (DEmiRs) encapsulated in serum-derived exosomes were screened via miRNA sequencing, the expression of which was verified through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-675-3p and clinicopathological features was investigated via the chi-squared test. The gain and loss of function of miR-675-3p in HCC cells were examined through transfection with mimics and inhibitor. Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays were conducted to test the biological effects of overexpressed and inhibited miR-675-3p on HCC cells in vitro. Tumor xenograft models and immunohistochemistry (IHC) were performed to assess the malignant progression of HCC cells with downregulated miR-675-3p in vivo.
Results: Uptake of exosomes from patients with HCC promoted the malignant phenotype of recipient cells. miRNA-675-3p within exosomes was confirmed to be upregulated in the serum of patients with HCC as compared with that of healthy donors. The chi-squared test results showed that miRNA-675-3p was associated with poor survival. Overexpression of miRNA-675-3p promoted the proliferation, invasion, and colony formation of HCC cells in vitro, while downregulation of miRNA-675-3p had the opposite biological effects on HCC cells and inhibited tumor growth and malignant progression in vivo. Furthermore, bioinformatics analysis indicated that miRNA-675-3p was involved in certain cellular processes, especially in lipid metabolism and regulation of several signaling pathways such as PI3K/AKT pathways and PPAR pathways.
Conclusions: miRNA-675-3p was upregulated in the serum of patients with HCC and exerted an oncogenic role in HCC cells via the targeting of downstream genes. These findings may constitute novel insights into the development of HCC, with miRNA-675-3p potentially serving as a biomarker for the diagnosis and treatment of patients with HCC.

Keywords: Exosome; biomarker; hepatocellular carcinoma (HCC); microRNA (miRNA); oncogene

DOI: https://doi.org/10.21037/tcr-2025-1372

Cell Mol Bioeng. 2025 Aug;18(3-4): 213-237

Engineered Extracellular Vesicles for Targeted Paclitaxel Delivery in Cancer Therapy: Advances, Challenges, and Prospects.

Mohamed J Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashishkumar Kyada, H Malathi, Deepak Nathiya, Deepak Bhanot, Waam Mohammed Taher, Mariem Alwan, Mahmood Jasem Jawad, Atheer Khdyair Hamad.

Scope: Extracellular vesicles (EVs) have emerged as promising cell-free delivery vehicles for cancer therapy due to their inherent biocompatibility, low immunogenicity, and natural targeting capabilities. EVs derived from various cellular sources offer distinct advantages in drug-loading capacity and therapeutic effectiveness. However, their clinical application is limited by challenges such as poor cargo stability, potential immunogenicity, and off-target effects. These limitations necessitate further surface functionalization of EVs to optimize vesicle stability, targeting precision, and safety of pharmacological cargos. Paclitaxel (PTX), a first-line chemotherapeutic agent effective against multiple cancers, is limited by poor solubility and significant systemic toxicity, highlighting the need for targeted delivery systems.
Methods: A literature search was conducted to identify relevant articles published between 1993 and 2025. This review provides a comprehensive overview of EV biogenesis and cellular origins, highlighting recent advances in engineering strategies for PTX delivery. Current progress in employing engineered EVs for PTX delivery in both in vitro and in vivo cancer models, along with practical challenges and future directions in the clinical translation of EV-based PTX delivery, are discussed.
Results: Preclinical studies demonstrate that engineered EVs can effectively encapsulate and deliver PTX to tumor sites, improving therapeutic outcomes while minimizing systemic side effects. Despite these advances, challenges remain in optimizing EV isolation, surface modification, PTX loading efficiency, and precise recognition of tumor cells.
Conclusion: Engineered EVs represent a promising platform for PTX delivery, combining targeted therapeutic potential with reduced systemic toxicity. Continued research to address technical and translational barriers will be critical for advancing EV-based PTX therapies toward clinical application.
Graphical Abstract:

Keywords: Bioengineering; Cancer; Drug delivery; Extracellular vesicles; Nanomedicine; Paclitaxel

DOI: https://doi.org/10.1007/s12195-025-00858-x

Cell Signal. 2025 Sep 17. pii: S0898-6568(25)00540-6. [Epub ahead of print] 112125

Rab27b-mediated CAFs derived exosomal miR-22-3p suppresses ferroptosis and promotes cisplatin resistance in osteosarcoma.

Wenyuan Duan, Xiaoying Niu, Yunsong Liu, Wen Tian.

Chemoresistance remains a significant hurdle in the cisplatin treatment of osteosarcoma, with poor patient outcomes. Cancer-associated fibroblasts (CAFs) and exosomes play crucial roles in this resistance by transferring miRNAs to cancer cells. In this study, we investigated the biological role of CAFs derived exosomal miR-22-3p in promoting chemoresistance. Using single-cell analysis and tissue exosome miRNAs sequencing, CAFs derived exosomal miR-22-3p was significantly associated with cisplatin resistance. Using various co-culture models, we showed the regulatory function of Rab27b and CAFs derived exosomal miR-22-3p, as well as the inhibitory effect of miR-22-3p on PTEN and ferroptosis. Experiments in vivo validated that CAFs derived exosomal miR-22-3p downregulated ferroptosis and promoted resistance to cisplatin. Overall, our findings suggest that targeting the Rab27b/exosomal miR-22-3p/PTEN/ferroptosis axis could be a promising therapeutic strategy for overcoming chemoresistance in osteosarcoma by providing critical insights into the role of exosome-mediated communication within the tumor microenvironment.

Keywords: CAFs derived exosomal miR-22-3p; Cisplatin resistance; Ferroptosis; PTEN; Rab27b

DOI: https://doi.org/10.1016/j.cellsig.2025.112125

Discov Oncol. 2025 Sep 15. 16(1): 1685

The involvement of exosomes in the tumorigenicity of breast cancer cell lines through the crosstalk between STAT3, Notch, and Wnt signaling pathways.

Shymaa Abdullah Mohamed, Toka M I Badawy, Menna Allah M K Hussein, Mohammed Salama, Yasser M El Kerm, Mohamed A Abdel Mohsen.

BACKGROUND: Exosomes play a critical role in the tumor microenvironment by interacting with signaling pathways that facilitate breast cancer metastasis, particularly the STAT3 pathway. The STAT3 pathway is essential for tumor progression and aggressiveness, as it interacts with other pathways like Wnt and Notch in particular, triple-negative breast cancer (TNBC) which is the most aggressive form of breast cancer, with a poor prognosis and rapid metastasis. It is exciting to researchers because it is therapeutically challenging and highly invasive. As a result of the lack of specific treatment options, conventional therapy is widely used, which frequently results in relapse.
OBJECTIVES: Elucidate the critical roles of exosomes in modulating breast cancer behaviour and disease progression in TNBC through STAT3 signaling pathways. Specifically, it was focused on the interplay between STAT3 and Wnt or Notch signaling MATERIALS AND METHODS: Exosomes were isolated from one TNBC patient and characterized using electron microscopy and the western blotting technique. This study utilized two subtypes of breast cancer cell lines: non-TNBC and TNBC. AG490 treatment inhibited STAT3 signaling, and then after inhibition, tumorigenic behaviours were evaluated. Gene expression profiles related to the investigated signaling pathways, Wnt and Notch, were detected.
THE RESULTS AND CONCLUSION: Exosomes significantly affect tumor behaviours and chemoresistance and manipulate signaling pathways associated with tumorigenesis, including Wnt/β-catenin and Notch. These results demonstrated the tumorigenic role of exosomes in the TNBC aggressiveness and suggest that their mechanisms may involve Wnt or Notch signaling mediated by the STAT3.

Keywords: Exosomes; Notch signaling pathway; STAT3 signaling pathway; Triple negative breast cancer; Tumorigenic behavior; Wnt signaling pathway

DOI: https://doi.org/10.1007/s12672-025-03334-0