bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–05–05
six papers selected by
Muhammad Rizwan, COMSATS University
  1. The hidden messengers: cancer associated fibroblasts-derived exosomal miRNAs as key regulators of cancer malignancy.
  2. Exosomal circ50547 as a potential marker and promotor of gastric cancer progression via miR-217/HNF1B axis.
  3. Bladder Cancer in Exosomal Perspective: Unraveling New Regulatory Mechanisms.
  4. Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view.
  5. Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.
  6. Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis.
  1. Front Cell Dev Biol. 2024 ;12 1378302
    The hidden messengers: cancer associated fibroblasts-derived exosomal miRNAs as key regulators of cancer malignancy.
    Zixuan Gou, Jiannan Li, Jianming Liu, Na Yang.
      Cancer-associated fibroblasts (CAFs), a class of stromal cells in the tumor microenvironment (TME), play a key role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis, and resistance to chemotherapy. CAFs mediate their activities by secreting soluble chemicals, releasing exosomes, and altering the extracellular matrix (ECM). Exosomes contain various biomolecules, such as nucleic acids, lipids, and proteins. microRNA (miRNA), a 22-26 nucleotide non-coding RNA, can regulate the cellular transcription processes. Studies have shown that miRNA-loaded exosomes secreted by CAFs engage in various regulatory communication networks with other TME constituents. This study focused on the roles of CAF-derived exosomal miRNAs in generating cancer malignant characteristics, including immune modulation, tumor growth, migration and invasion, epithelial-mesenchymal transition (EMT), and treatment resistance. This study thoroughly examines miRNA's dual regulatory roles in promoting and suppressing cancer. Thus, changes in the CAF-derived exosomal miRNAs can be used as biomarkers for the diagnosis and prognosis of patients, and their specificity can be used to develop newer therapies. This review also discusses the pressing problems that require immediate attention, aiming to inspire researchers to explore more novel avenues in this field.
    Keywords:  cancer malignant characteristics; cancer-associated fibroblasts-derived exosomal miRNA; diagnosis; dual regulatory functions; prognosis; therapy
    DOI:  https://doi.org/10.3389/fcell.2024.1378302
  2. Transl Oncol. 2024 Apr 30. pii: S1936-5233(24)00096-2. [Epub ahead of print]45 101969
    Exosomal circ50547 as a potential marker and promotor of gastric cancer progression via miR-217/HNF1B axis.
    Xueyan Zang, Rongrong Wang, Ziyi Wang, Shuangyang Qiu, Fan Zhang, Le Zhou, Ye Shen, Hui Qian, Wenrong Xu, Jiajia Jiang.
       BACKGROUND: Exosomes, one of small extracellular vesicles, play a vital role in cell to cell communication and contribute to the advancement of tumors through their cargo molecules. Exosomal circRNAs have emerged as significant players in various types of tumors. Thus, this study aimed to investigate how exosomal circRNAs are involved in the diagnosis and progression of gastric cancer (GC).
    METHODS: Serum exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis and Western blot. CCK-8, colony formation and transwell assays were conducted to study the function of hsa_circ_0050547 (named as circ50547). qRT-PCR was used to quantify the expression of circ50547 in GC tissues and serum exosomes. Fluorescence in situ hybridization was applied to detect the cellular distribution of circ50547. Stemness and drug-resistance were detected by sphere formation, WB, flow cytometry and half-maximal inhibitory concentration analyses. Bioinformatic analyses, luciferase experiments, qRT-PCR and WB were used to investigate molecular mechanisms.
    RESULTS: We discovered for the first time a new type of GC-derived exosomal circRNA, circ50547. We found that circ50547 is highly expressed in both GC tissues and serum exosomes. Interestingly, we observed that the diagnostic value of exosomal circ50547 is superior to that of serum circ50547. Circ50547 overexpression enhanced the proliferation, migration, invasion, stemness and drug resistance of GC cells, while knockdown of circ50547 showed the opposite effect. Mechanistically, circ50547 acted as a sponge for miR-217 to regulate the expression of HNF1B, which promoted gastric cancer progression.
    CONCLUSION: Exosomal circ50547 may be a promising marker for the diagnosis and prognosis prediction of GC. These findings suggest that it plays an oncogenic role through miR-217/HNF1B signaling pathway in GC.
    Keywords:  CircRNAs; Exosomes; Gastric cancer; Stem，Resistance; miRNA
    DOI:  https://doi.org/10.1016/j.tranon.2024.101969
  3. Int J Nanomedicine. 2024 ;19 3677-3695
    Bladder Cancer in Exosomal Perspective: Unraveling New Regulatory Mechanisms.
    Cong Yin, Cen Liufu, Tao Zhu, Shuai Ye, Jiahao Jiang, Mingxia Wang, Yan Wang, Bentao Shi.
      Bladder cancer, a prevalent malignant neoplasm of the urinary tract, exhibits escalating morbidity and mortality rates. Current diagnosis standards rely on invasive and costly cystoscopy and histopathology, underscoring the urgency for non-invasive, high-throughput, and cost-effective novel diagnostic techniques to ensure timely detection and standardized treatment. Recent years have witnessed the rise of exosome research in bladder cancer studies. Exosomes contain abundant bioactive molecules that can help elucidate the intricate mechanisms underlying bladder cancer pathogenesis and metastasis. Exosomes hold potential as biomarkers for early bladder cancer diagnosis while also serving as targeted drug delivery vehicles to enhance treatment efficacy and mitigate adverse effects. Furthermore, exosome analyses offer insights into the complex molecular signaling networks implicated in bladder cancer progression, revealing novel therapeutic targets. This review provides a comprehensive overview of prevalent exosome isolation techniques and highlights the promising clinical utility of exosomes in both diagnostic and therapeutic applications in bladder cancer management.
    Keywords:  biomarkers; bladder cancer; exosomes; isolation methods; treatment
    DOI:  https://doi.org/10.2147/IJN.S458397
  4. Int Immunopharmacol. 2024 May 02. pii: S1567-5769(24)00689-1. [Epub ahead of print]134 112171
    Mesenchymal stem cell-derived exosomes for management of prostate cancer: An updated view.
    Fahimeh Lavi Arab, Akram Hoseinzadeh, Fatemeh Hafizi, Fatemeh Sadat Mohammadi, Farid Zeynali, Melika Hadad Tehran, Amirreza Rostami.
      Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.
    Keywords:  Exosomes; Mesenchymal stem cells; Prostate cancer; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.intimp.2024.112171
  5. Sci Rep. 2024 May 02. 14(1): 10075
    Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.
    Masahiro Makinoya, Kozo Miyatani, Yoshiaki Matsumi, Yu Sakano, Shota Shimizu, Yuji Shishido, Takehiko Hanaki, Kyoichi Kihara, Tomoyuki Matsunaga, Manabu Yamamoto, Naruo Tokuyasu, Shuichi Takano, Teruhisa Sakamoto, Toshimichi Hasegawa, Hiroaki Saito, Yuji Nakayama, Mitsuhiko Osaki, Futoshi Okada, Yoshiyuki Fujiwara.
      Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.
    DOI:  https://doi.org/10.1038/s41598-024-60967-x
  6. Front Oncol. 2024 ;14 1357248
    Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis.
    Yuxuan Cao, Xinbo Liu, Jiayi Liu, Ziyi Su, Wenxuan Liu, Lei Yang, Liwen Zhang.
       Background: Lung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis.
    Methods: For this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed.
    Results: The study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86.
    Conclusion: Our study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers.
    Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.
    Keywords:  circRNA; exosome; lncRNA; lung cancer; miRNA
    DOI:  https://doi.org/10.3389/fonc.2024.1357248
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