bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–09–29
nine papers selected by
Muhammad Rizwan, COMSATS University



  1. Biochim Biophys Acta Rev Cancer. 2024 Sep 21. pii: S0304-419X(24)00119-7. [Epub ahead of print]1879(6): 189188
      Exosomes, extracellular vesicles carrying a cargo rich in various non-coding RNAs (ncRNAs), have emerged as crucial mediators of intercellular communication. Their stability, abundance, and specificity make exosomal ncRNAs promising candidates for biomarker discovery. The discovery of exosomal ncRNAs has unveiled a novel avenue for the exploration of biomarkers in tumor early diagnosis. This review consolidates current knowledge on the role of exosomal ncRNAs as potential biomarkers in the early detection of various tumors. We provide an overview of recent studies demonstrating the diagnostic potential of exosomal ncRNAs across multiple cancer types, highlighting their sensitivity, specificity, and feasibility for early detection. This review underscores the potential of exosomal ncRNAs as non-invasive biomarkers for early tumor diagnosis, paving the way for improved clinical outcomes through timely intervention and personalized management strategies.
    Keywords:  Biomarkers; Exosomes; Non-coding RNAs; Tumor early diagnosis
    DOI:  https://doi.org/10.1016/j.bbcan.2024.189188
  2. RSC Adv. 2024 Sep 24. 14(42): 30807-30829
      Exosomes are a subpopulation of extracellular vesicles (EVs) that naturally originate from endosomes. They play a significant role in cellular communication. Tumor-secreted exosomes play a crucial role in cancer development and significantly contribute to tumorigenesis, angiogenesis, and metastasis by intracellular communication. Tumor-derived exosomes (TEXs) are a promising biomarker source of cancer detection in the early stages. On the other hand, they offer revolutionary cutting-edge approaches to cancer therapeutics. Exosomes offer a cell-free approach to cancer therapeutics, which overcomes immune cell and stem cell therapeutics-based limitations (complication, toxicity, and cost of treatment). There are multiple sources of therapeutic exosomes present (stem cells, immune cells, plant cells, and synthetic and modified exosomes). This article explores the dynamic source of exosomes (plants, mesenchymal stem cells, and immune cells) and their modification (chimeric, hybrid exosomes, exosome-based CRISPR, and drug delivery) based on cancer therapeutic development. This review also highlights exosomes based clinical trials and the challenges and future orientation of exosome research. We hope that this article will inspire researchers to further explore exosome-based cancer therapeutic platforms for precision oncology.
    DOI:  https://doi.org/10.1039/d4ra04512b
  3. Oncol Res. 2024 ;32(10): 1649-1660
      Exosomes, minute vesicles ubiquitously released by diverse cell types, serve as critical mediators in intercellular communication. Their pathophysiological relevance, especially in malignancies, has garnered significant attention. A meticulous exploration of the exosomal impact on cancer development has unveiled avenues for innovative and clinically valuable techniques. The cargo conveyed by exosomes exerts transformative effects on both local and distant microenvironments, thereby influencing a broad spectrum of biological responses in recipient cells. These membrane-bound extracellular vesicles (EVs) play a pivotal role in delivering bioactive molecules among cells and organs. Cellular and biological processes in recipient cells, ranging from stromal cell reprogramming to immunological responses, extracellular matrix formation, and modulation of cancer cell activation, expansion, and metastasis, are subject to exosome-mediated cell-to-cell communication. Moreover, exosomes have been implicated in endowing cancer cells with resistance to treatment. Extensive research has explored the potential of exosomes as therapeutic targets and diagnostic indicators. This comprehensive review seeks to provide an in-depth understanding of the pivotal components and roles of exosomes in tumorigenesis, growth, progression, and therapeutic responses. The insights into the multifaceted involvement of exosomes in malignant cancers are essential for the scientific community, fostering the development of novel therapeutic and diagnostic strategies in the relentless pursuit of cancer.
    Keywords:  Adipose tissue; Exosomes; Extracellular vesicles; Obesity; Tumor microenvironment
    DOI:  https://doi.org/10.32604/or.2024.043482
  4. Biomarkers. 2024 Sep 24. 1-12
       BACKGROUND: Breast cancer (BC) is one of the most common malignancies in women. Exosomes are widely found in body fluids and carry microRNAs (miRNAs) that reflect the biological properties of the parental cells. Our study aimed to investigate the differential expression of miR-200c in breast cancer serum exosomes and its diagnostic value.
    METHODOLOGY: miRNA profiles in culture supernatant exosomes of normal mammary epithelial cells MCF-10A and BC cells (MCF-7,MDA-MB-231, MCF-7 Taxol) were examined by miRNA deep sequencing to screen for significantly differentially expressed miRNAs; Transmission electron microscopy (TEM), Nanoparticle tracking analysis (NTA), and Western blot were used to identify exosomes; qPCR was used to detect the expression level of miR-200c in cellular exosomes and serum exosomes; The efficacy of individual and combined tests of each indicator to diagnose BC was evaluated using receiver operating characteristic (ROC) curves.
    RESULTS: We identified typical exosome features by TEM, NTA and Western blot, indicating successful exosome extraction. Then our miRNA sequencing results and qRT-PCR experiments showed that miR-200c was significantly down-regulated in BC cell exosomes. In addition, we divided the clinical serum samples into two cohorts according to region, and in independent cohort I, the serum exosomal miR-200c levels of BC patients were significantly lower than those of healthy controls. In cohort II, serum exosomal miR-200c expression was significantly lower in the BC group than in the control and benign breast disease (BBD) groups, whereas miR-200c expression in the BBD group was not statistically different from that in the control group. ROC analyses in both independent cohorts confirmed that serum exosomal miR-200c could differentiate between patients with and without breast cancer disease and could be used as an early diagnostic marker for breast cancer disease.
    CONCLUSION: Serum exosome miR-200c can be used as a potential biomarker for the diagnosis of BC, and combined with conventional serum diagnostic markers AFP, CA125 and CA153 can help to improve diagnostic efficiency.
    Keywords:  ROC; breast cancer (BC); diagnostic biomarker; miR-200c; serum exosomes
    DOI:  https://doi.org/10.1080/1354750X.2024.2406520
  5. Int J Pharm. 2024 Sep 18. pii: S0378-5173(24)00966-9. [Epub ahead of print] 124732
      As people's living standards continue to improve and human life span expectancy increases, the incidence and mortality rates of breast cancer are continuously rising. Early detection of breast cancer and targeted therapy for different breast cancer subtypes can significantly reduce the mortality rate and alleviate the suffering of patients. Exosomes are extracellular vesicles secreted by various cells in the body. They participate in physiological and pathological responses by releasing active substances and play an important role in regulating intercellular communication. In recent years, research on exosomes has gradually expanded, and their special membrane structure and targetable characteristics are being increasingly applied in various clinical studies. Mesenchymal stem cells (MSCs)-derived exosomes play an important role in regulating the progression of breast cancer. In this review, we summarize the current treatment methods for breast cancer, the connection between MSCs, exosomes, and breast cancer, as well as the application of exosomes derived from MSCs from different sources in cancer treatment. We highlight how the rational design of modified MSCs-derived exosomes (MSCs-Exos) delivery systems can overcome the uncertainties of stem cell therapy and overcome the clinical translation challenges of nanomaterials. This work aims to promote future research on the application of MSCs-Exos in breast cancer treatment.
    Keywords:  Breast cancer; Drug delivery; Exosomes; Gene editing; Mesenchymal stem cells
    DOI:  https://doi.org/10.1016/j.ijpharm.2024.124732
  6. Oncol Res. 2024 ;32(10): 1623-1635
       Background: Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation.
    Methods: Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.
    Results: let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.
    Conclusion: Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.
    Keywords:  Exosomal microRNA; Gene expression profiling; Oral cancer; TAGLN; Tumorigenesis biomarkers; let-7c-5p
    DOI:  https://doi.org/10.32604/or.2024.048191
  7. Cells. 2024 Sep 17. pii: 1562. [Epub ahead of print]13(18):
      A growing number of studies have shown that microRNAs (miRNAs) can exert oncogenic or tumor suppressor activities in a variety of cancers, including lung cancer. Given their presence in exosome preparations, microRNA molecules may in fact participate in exosomal intercellular transfers and signaling. In the present study, we examined the profile of 25 circulating exosomal microRNAs in ostensibly healthy controls compared to patients with squamous cell lung cancers (SQCLC) or lung adenocarcinomas (LUAD). Eight miRNAs, namely, miR-21-5p, miR-126-3p, miR-210-3p, miR-221-3p, Let-7b-5p, miR-146a-5p, miR-222-3p, and miR-9-5p, were highly enriched in the cohort and selected for further analyses. All miRNAs were readily detected in non-small cell lung cancer (NSCLC) patients of both sexes at all cancer stages, and their levels in exosomes correlated with the clinicopathological characteristics of tumors. Thus, the presence of these miRNAs in circulating exosomes may contribute to the regulation of oncogenic activity in patients with NSCLC.
    Keywords:  NSCLC; diagnostic performance; exosomes; gene ontology; miRNAs
    DOI:  https://doi.org/10.3390/cells13181562
  8. Breast Cancer (Dove Med Press). 2024 ;16 631-643
       Background: Timely detection of tumor progression in breast cancer (BC) patients is critical for therapeutic management and prognosis. Plasma exosomal miRNAs are potential liquid biopsy markers for monitoring tumor progression, but their roles in BC remain unclear.
    Methods: In the TCGA database, we first screened for miRNAs significantly associated with BC progression by comparing miRNA expression in para-carcinoma tissues, stage I BC tissues, and stage II-III BC tissues (n = 1026). Cox regression analyses and survival analyses were performed on candidate miRNAs to explore their prognostic value (n = 848). KEGG, GO, and PPI analyses were used to identify enriched pathways associated with cancer. Finally, the potential of candidate miRNAs as liquid biopsy markers was evaluated by sequencing and analyzing plasma exosomal miRNAs from our collection of 45 BC patients (14 in stage I, 31 in stage II-III) and 5 healthy controls, combined with qRT-PCR analysis to assess the correlation of candidate gene expression in plasma exosomes and BC tissues.
    Results: We found that only miR-203a-3p was progressively elevated with BC progression and was associated with poor prognosis in the TCGA dataset. Its potential target genes were enriched in pathways related to tumor progression, and the downregulation of 48 of these genes was associated with poor prognosis. More importantly, plasma exosomal miR-203a-3p was also found to gradually increase with BC progression, and its expression was positively correlated with miR-203a-3p in BC tissues. This result suggests that plasma exosomal miR-203a-3p may reflect the expression of miR-203a-3p in tumor tissues and serve as a potential liquid biopsy marker for monitoring BC progressions.
    Conclusion: We found for the first time that elevated miR-203a-3p was associated with BC progression and poor prognosis. Our findings suggested that plasma exosomal miR-203a-3p could hold potential as a liquid biopsy marker for evaluating BC progression in patients.
    Keywords:  breast cancer; liquid biopsy marker; plasma exosomal miR-203a-3p; tumor progression
    DOI:  https://doi.org/10.2147/BCTT.S478328
  9. Ir J Med Sci. 2024 Sep 26.
       BACKGROUND: Gastric cancer (GC) is a significant global health concern, ranking as the fifth most common cancer and the third leading cause of cancer-related deaths. The role of miR-502-5p in various cancers has been studied, but its specific impact on gastric cancer through exosomes is not well understood. This study aimed to investigate the role and mechanism of exosome-derived miR-502-5p in gastric cancer.
    METHODS: Differential expression of miR-502-5p in tissues or serum of GC patients was determined using qRT-PCR. The impact of miR-502-5p on cell proliferation, migration, and invasion was assessed through in vitro and in vivo experiments. The potential of exosome-miR-502-5p to inhibit metastatic ability was also explored by using vivo and vitro assay. Furthermore, the underlying mechanism of miR-502-5p in gastric cancer was investigated using western blotting.
    RESULTS: It was found that miR-502-5p suppressed the proliferation, migration, and invasion of gastric cancer cells. Exosome-miR-502-5p expression was negatively linked to metastatic ability and demonstrated inhibition of metastasis in vitro and in vivo. Additionally, miR-502-5p appeared to inhibit angiogenesis through the Wnt/β-catenin pathway in gastric cancer.
    CONCLUSIONS: Exosomal miR-502-5p acts as a suppressor in the development and progression of gastric cancer, suggesting its potential as a target for anti-cancer therapy or as a diagnostic biomarker.
    Keywords:  Angiogenesis; Exosomes; Gastric cancer; MiR-502-5p; Wnt/β-catenin
    DOI:  https://doi.org/10.1007/s11845-024-03789-0