bims-exocan 2023-12-03 papers

Issue of 2023–12–03
five papers selected by
Muhammad Rizwan, COMSATS University

Breast Cancer (Dove Med Press). 2023 ;15 825-840

The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications.

Jie Li, Dejiao He, Yajun Bi, Shengxuan Liu.

Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20-23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

Keywords: breast cancer; detection; exosome; miRNAs; therapy; tumor microenvironment

DOI: https://doi.org/10.2147/BCTT.S432750

J Ovarian Res. 2023 Nov 29. 16(1): 232

Proteomic analysis of exosomes secreted during the epithelial-mesenchymal transition and potential biomarkers of mesenchymal high-grade serous ovarian carcinoma.

Germano Aguiar Ferreira, Carolina Hassibe Thomé, Clarice Izumi, Mariana Lopes Grassi, Guilherme Pauperio Lanfredi, Marcus Smolka, Vitor Marcel Faça, Francisco José Candido Dos Reis.

BACKGROUND: The epithelial-mesenchymal transition (EMT) promotes cell signaling and morphology alterations, contributing to cancer progression. Exosomes, extracellular vesicles containing proteins involved in cell-cell communication, have emerged as a potential source of biomarkers for several diseases.
METHODS: Our aim was to assess the proteome content of exosomes secreted after EMT-induction to identify potential biomarkers for ovarian cancer classification. EMT was induced in the ovarian cancer cell line CAOV3 by treating it with EGF (10 ng/mL) for 96 h following 24 h of serum deprivation. Subsequently, exosomes were isolated from the supernatant using selective centrifugation after decellularization, and their characteristics were determined. The proteins present in the exosomes were extracted, identified, and quantified using Label-Free-Quantification (LFQ) via Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). To identify potential biomarkers, the obtained proteomic data was integrated with the TGGA database for mRNA expression using principal component analysis and a conditional inference tree.
RESULTS: The exosomes derived from CAOV3 cells exhibited similar diameter and morphology, measuring approximately 150 nm, regardless of whether they were subjected to EMT stimulation or not. The proteomic analysis of proteins from CAOV3-derived exosomes revealed significant differential regulation of 157 proteins, with 100 showing upregulation and 57 downregulation upon EMT induction. Further comparison of the upregulated proteins with the TCGA transcriptomic data identified PLAU, LAMB1, COL6A1, and TGFB1 as potential biomarkers of the mesenchymal HGSOC subtype.
CONCLUSIONS: The induction of EMT, the isolation of exosomes, and the subsequent proteomic analysis highlight potential biomarkers for an aggressive ovarian cancer subtype. Further investigation into the role of these proteins is warranted to enhance our understanding of ovarian cancer outcomes.

Keywords: Epithelial-mesenchymal transition; Exosomes; Extracellular vesicles; Ovarian cancer; Secretome

DOI: https://doi.org/10.1186/s13048-023-01304-0

Front Immunol. 2023 ;14 1296857

Recent advances in exosome-based immunotherapy applied to cancer.

Jindong Xie, Zihan Zheng, Ling Tuo, Xinpei Deng, Hailin Tang, Cheng Peng, Yutian Zou.

Cancer stands as a prominent contributor to global mortality rates, necessitating immediate attention toward the exploration of its treatment options. Extracellular vesicles have been investigated as a potential cancer therapy in recent years. Among them, exosomes, as cell-derived nanovesicles with functions such as immunogenicity and molecular transfer, offer new possibilities for immunotherapy of cancer. However, multiple studies have shown that exosomes of different cellular origins have different therapeutic effects. The immunomodulatory effects of exosomes include but are not limited to inhibiting or promoting the onset of immune responses, regulating the function of molecular signaling pathways, and serving as carriers of antitumor drugs. Therefore, this mini-review attempts to summarize and evaluate the development of strategies for using exosomes to package exogenous cargos to promote immunotherapy in cancer.

Keywords: biomarker; cancer; exosome; immune cells; immunotherapy

DOI: https://doi.org/10.3389/fimmu.2023.1296857

ACS Omega. 2023 Nov 21. 8(46): 43374-43387

Research Advances of Engineered Exosomes as Drug Delivery Carrier.

Lianghui Huang, Enguang Wu, Jiawei Liao, Zongyi Wei, Jin Wang, Zhenhua Chen.

Exosomes are nanoscale vesicles secreted by living cells that have similar membrane composition to parental cells and carry a variety of proteins, lipids, and nucleic acids. Therefore, exosomes have certain biological activities and play an important role in intercellular communication. On the basis of its potential as a carrier for drug delivery systems, exosomes have been engineered to compensate for the shortage of natural exosomes through various engineering strategies for improving drug delivery efficiency, enhancing targeting to tissues and organs, and extending the circulating half-life of exosomes. This review focuses on the engineered exosomes loading drugs through different strategies, discussions on exosome surface modification strategies, and summarizes the advantages and disadvantages of different strategies. In addition, this review provides an overview of the recent applications of engineered exosomes in a number of refractory and relapsable diseases. This review has the potential to provide a reference for further research and development of engineered exosomes.

DOI: https://doi.org/10.1021/acsomega.3c04479

Front Genet. 2023 ;14 1249678

Comparative analyses of salivary exosomal miRNAs for patients with or without lung cancer.

Mengfeng Liu, Xiran Yu, Jianlong Bu, Qifan Xiao, Sitong Ma, Naozhong Chen, Changfa Qu.

Introduction: Lung cancer is the most frequent cause of cancer-related deaths worldwide. Exosomes are involved in different types of cancer, including lung cancer. Methods: We collected saliva from patients with (LC) or without (NC) lung cancer and successfully isolated salivary exosomes by ultracentrifugation. MiRNA sequencing was implemented for the exosome samples from NC and LC groups, dgeR was used to determine differentially expressed miRNAs (DE miRNAs), and quantitative real-time polymerase chain reaction (qPCR) was used to verify three differentially expressed microRNAs (miRNAs). Results: A total of 372 miRNAs were identified based on the sequencing results. Subsequently, 15 DE miRNAs were identified in LC vs. NC, including eight upregulated miRNAs and seven downregulated miRNAs. Some DE miRNAs were validated via qPCR. A total of 488 putative target genes of the upregulated DE miRNAs were found, and the functional analyses indicated that numerous target genes were enriched in the pathways associated with cancer. Discussion: This suggests that miRNAs of salivary exosomes might have the potential to be used as biomarkers for prediction and diagnosis of lung cancer.

Keywords: biomarker; exosome; lung cancer; miRNA sequencing; microRNA; saliva

DOI: https://doi.org/10.3389/fgene.2023.1249678