bims-exocan 2024-04-21 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–04–21
eight papers selected by
Muhammad Rizwan, COMSATS University

Exosomal long non-coding RNAs in cancer: Interplay, modulation, and therapeutic avenues.
Current knowledge on therapeutic, diagnostic, and prognostics applications of exosomes in multiple myeloma: Opportunities and challenges.
Circulating tumor cell-derived exosome-transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells.
M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.
Application of exosomes in tumor immunity: recent progresses.
Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.
Harnessing HEK293 cell-derived exosomes for hsa-miR-365a-3p delivery: Potential application in hepatocellular carcinoma therapy.
Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.

Noncoding RNA Res. 2024 Sep;9(3): 887-900

Exosomal long non-coding RNAs in cancer: Interplay, modulation, and therapeutic avenues.

Rahaba Marima, Afra Basera, Thabiso Miya, Botle Precious Damane, Jeyalakshmi Kandhavelu, Sheefa Mirza, Clement Penny, Zodwa Dlamini.

  In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.

Keywords:  Biomarkers; Cancer; Exosomal lncRNAs; Exosomes; Intercellular and intracellular communication

DOI:  https://doi.org/10.1016/j.ncrna.2024.03.014
Arch Biochem Biophys. 2024 Apr 16. pii: S0003-9861(24)00113-9. [Epub ahead of print]756 109994

Current knowledge on therapeutic, diagnostic, and prognostics applications of exosomes in multiple myeloma: Opportunities and challenges.

Aghdas Ramezani, Aida Tafazoli, Fatemeh Salimi, Mahlegha Ghavami, Hanie Arjmandi, Bahman Khalesi, Zahra Sadat Hashemi, Saeed Khalili.

  Interactions between the plasma cells and the BM microenvironment of Multiple myeloma (MM) take place through factors such as exosomes. Many studies have confirmed the role of exosomes in these interactions. By carrying proteins, cytokines, lipids, microRNAs, etc. as their cargo, exosomes can regulate the interactions between MM plasma cells and neighboring cells and participate in the signaling between cancer cells and the environment. It has been shown that MM-derived exosomes can induce angiogenesis, enhance osteoblast activity, confer drug resistance, and have immunosuppressive properties. Abnormal cargos in endosomes originating from MM patients, can be used as a cancer biomarker to detect or screen early prognosis in MM patients. The native nanostructure of exosomes, in addition to their biocompatibility, stability, and safety, make them excellent candidates for therapeutic, drug delivery, and immunomodulatory applications against MM. On the other hand, exosomes derived from dendritic cells (DC) may be used as vaccines against MM. Thanks to the development of new 'omics' approaches, we anticipate to hear more about exosomes in fight against MM. In the present review, we described the most current knowledge on the role of exosomes in MM pathogenesis and their potential role as novel biomarkers and therapeutic tools in MM.

Keywords:  Diagnosis; Exosome; Multiple myeloma; Prognosis; Targeted drug delivery

DOI:  https://doi.org/10.1016/j.abb.2024.109994
J Nanobiotechnology. 2024 Apr 18. 22(1): 191

Circulating tumor cell-derived exosome-transmitted long non-coding RNA TTN-AS1 can promote the proliferation and migration of cholangiocarcinoma cells.

Xu Zhou, Xiaohan Kong, Jun Lu, Heng Wang, Meng Liu, Shuchao Zhao, Zhaozhi Xia, Qinggong Liu, Hongrui Sun, Xin Gao, Chaoqun Ma, Zheyu Niu, Faji Yang, Xie Song, Hengjun Gao, Shizhe Zhang, Huaqiang Zhu.

   BACKGROUND: Exosomes assume a pivotal role as essential mediators of intercellular communication within tumor microenvironments. Within this context, long noncoding RNAs (LncRNAs) have been observed to be preferentially sorted into exosomes, thus exerting regulatory control over the initiation and progression of cancer through diverse mechanisms.
RESULTS: Exosomes were successfully isolated from cholangiocarcinoma (CCA) CTCs organoid and healthy human serum. Notably, the LncRNA titin-antisense RNA1 (TTN-AS1) exhibited a conspicuous up-regulation within CCA CTCs organoid derived exosomes. Furthermore, a significant elevation of TTN-AS1 expression was observed in tumor tissues, as well as in blood and serum exosomes from patients afflicted with CCA. Importantly, this hightened TTN-AS1 expression in serum exosomes of CCA patients manifested a strong correlation with both lymph node metastasis and TNM staging. Remarkably, both CCA CTCs organoid-derived exosomes and CCA cells-derived exosomes featuring pronounced TTN-AS1 expression demonstrated the capability to the proliferation and migratory potential of CCA cells. Validation of these outcomes was conducted in vivo experiments.
CONCLUSIONS: In conclusion, our study elucidating that CCA CTCs-derived exosomes possess the capacity to bolster the metastasis tendencies of CCA cells by transporting TTN-AS1. These observations underscore the potential of TTN-AS1 within CTCs-derived exosomes to serve as a promising biomarker for the diagnosis and therapeutic management of CCA.

Keywords:  Cholangiocarcinoma; Circulating tumor cells; Exosome; Metastasis; Titin-antisense RNA1

DOI:  https://doi.org/10.1186/s12951-024-02459-8
Adv Sci (Weinh). 2024 Apr 19. e2309298

M2 Tumor-Associated Macrophages-Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression.

Yanzheng Wang, Jiahui Zhang, Hui Shi, Maoye Wang, Dan Yu, Min Fu, Yu Qian, Xiaoxin Zhang, Runbi Ji, Shouyu Wang, Jianmei Gu, Xu Zhang.

  M2-polarized tumor-associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs-derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis-dependent manner. It is identified that MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ-catenin protein and suppressed its ubiquitination and degradation by β-TRCP. In addition, MALAT1 upregulated HIF-1α expression by acting as a sponge for miR-217-5p. The activation of β-catenin and HIF-1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual-targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome-mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs-derived exosomes promote gastric cancer progression via MALAT1-mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Keywords:  MALAT1; exosomes; gastric cancer; glycolysis; tumor‐associated macrophages

DOI:  https://doi.org/10.1002/advs.202309298
Front Cell Dev Biol. 2024 ;12 1372847

Application of exosomes in tumor immunity: recent progresses.

Haiyan Qiu, Junting Liang, Guang Yang, Zhenyu Xie, Zhenpeng Wang, Liyan Wang, Jingying Zhang, Himansu Sekhar Nanda, Hui Zhou, Yong Huang, Xinsheng Peng, Chengyu Lu, Huizhi Chen, Yubin Zhou.

  Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

Keywords:  drug delivery; exosomes; extracellular vesicles; immunoregulation; tumor immunity

DOI:  https://doi.org/10.3389/fcell.2024.1372847
Cell Signal. 2024 Apr 17. pii: S0898-6568(24)00150-5. [Epub ahead of print] 111182

Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Zhimei Sheng, Xuejie Wang, Xiaodi Ding, Yuanhang Zheng, Ai Guo, Jiayu Cui, Jing Ma, Wanli Duan, Hao Dong, Hongxing Zhang, Meimei Cui, Wenxia Su, Baogang Zhang.

  Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

Keywords:  Breast cancer; Cancer-associated fibroblast; Exosomes; G3BP2; miR-92a

DOI:  https://doi.org/10.1016/j.cellsig.2024.111182
Heliyon. 2024 Apr 30. 10(8): e29333

Harnessing HEK293 cell-derived exosomes for hsa-miR-365a-3p delivery: Potential application in hepatocellular carcinoma therapy.

Armita Ghotaslou, Arezou Azizsoltani, Kaveh Baghaei, Effat Alizadeh.

  Hepatocellular carcinoma (HCC) is the most frequent form of liver malignancy, and curing it is very challenging. Restoring tumor suppressor microRNAs could trigger the initiation of cellular anticancer mechanisms. Exosomes are nanosized biocarriers capable of fusing with cell membranes and delivering their cargo. The main goal of the current study was to explore the potential of human embryonic kidney cells (HEK293) cell-derived exosomes to provide an anticancer therapy based on the restoration of tumor suppressor miR-365a downregulated in HepG2 cells. To accomplish this aim, exosomes were isolated from the HEK293 cell line culture and characterized, enriched by Homo sapiens (hsa) miR-365a-3p mimics. Exosomes enabled an efficient loading and intracellular delivery of hsa-miR-365a mimics, which translated into G0/G1 cell cycle arrest, induction of oxidative stress, reduction of migration capacity, and high apoptosis rate. The findings indicate that the delivery of miR-365a-3p by HEK293-derived exosomes may act as an innovative and effective therapeutic strategy against HCC.

Keywords:  Cell cycle; Exosome; HEK293; HepG2; MiR-365a-3p mimic; Nrf2; ROS

DOI:  https://doi.org/10.1016/j.heliyon.2024.e29333
Sci Rep. 2024 04 17. 14(1): 8902

Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.

Tahani Bakhsh, Safiah Alhazmi, Ali Farsi, Abdulaziz S Yusuf, Amani Alharthi, Safa H Qahl, Maha Ali Alghamdi, Faisal A Alzahrani, Ola H Elgaddar, Mohanad A Ibrahim, Ahmed Bahieldin.

  Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor β (TGFβ) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.

Keywords:  Biomarkers; Colorectal cancer; Deep sequencing; Exosomes; miRNAs

DOI:  https://doi.org/10.1038/s41598-024-58536-3