bims-exocan 2024-10-13 papers

Issue of 2024–10–13
six papers selected by
Muhammad Rizwan, COMSATS University

Curr Top Membr. 2024 ;pii: S1063-5823(24)00018-8. [Epub ahead of print]94 247-285

The role of extracellular vesicles in cancer.

Elizabeth Cristina Perez Hurtado, Juan Sebastian Henao Agudelo, Rodrigo Augusto Foganholi da Silva, Thiago Albuquerque Viração, Célio Junior da Costa Fernandes.

Extracellular vesicles (EVs), which include small EVs such as exosomes, play a critical role in intercellular communication and are produced by both cancer and non-cancer cells. Several studies have shown that cancer cells exploit various strategies to regulate the biogenesis, composition, and functions of EVs primarily to promote cancer progression. Given that exosomes originate from major sorting hubs at the limiting membrane of endosomes, they are central to a signaling network that connects external stimuli with intrinsic tumor cell features. Exosomes contain diverse repertoires of molecular cargos, such as proteins, lipids, and nucleic acids, which determine their heterogeneity and functional properties in cancer progression. Therefore, targeting exosome biogenesis will enhance our understanding of tumorigenesis and also promote the discovery of novel approaches for cancer therapy. In this chapter we summarize the machinery of exosome biogenesis and the local, distant, and systemic effects of exosomes released by cancer cells. Furthermore, we explore how these exosomes regulate the anti-tumor immune response and epigenetic mechanisms to sustain cancer progression and their implications in cancer prevention and treatment.

Keywords: Cancer progression; Cancer therapy; Cell communication; Epigenetic modifiers; Exosome; Immune surveillance; MicroRNAs; Rabs proteins; Small extracellular vesicles; Tumor microenvironment

DOI: https://doi.org/10.1016/bs.ctm.2024.06.010

J Exp Clin Cancer Res. 2024 Oct 09. 43(1): 281

Exosomal miR-106a-5p from highly metastatic colorectal cancer cells drives liver metastasis by inducing macrophage M2 polarization in the tumor microenvironment.

Yahang Liang, Junyu Li, Yuli Yuan, Houqiong Ju, Hualin Liao, Mingming Li, Yang Liu, Yao Yao, Lingling Yang, Taiyuan Li, Xiong Lei.

BACKGROUND: The tumor microenvironment (TME) is a dynamic system orchestrated by intricate cell-to-cell crosstalk. Specifically, macrophages within the TME play a crucial role in driving tumor progression. Exosomes are key mediators of communication between tumor cells and the TME. However, the mechanisms underlying exosome-driven crosstalk between tumor cells and macrophages during colorectal cancer (CRC) progression remain incompletely elucidated.
METHODS: Single-cell RNA sequencing were analyzed using the Seurat package. Exosomes were isolated using ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. miRNAs differentially expressed in exosomes were analyzed using the limma package. CD206 expression in CRC tissues, exosomes tracing, and exosomal miR-106a-5p transport were observed through immunofluorescence. Macrophage polarization was assessed via qRT-PCR, ELISA, and flow cytometry. The interactions between miR-106a-5p, hnRNPA1, and SOCS6 were evaluated using miRNA pull-down, RIP, and dual-luciferase reporter assays. Transwell assays and liver metastasis model explored the role of exosomal miR-106a-5p-induced M2 macrophages in promoting CRC liver metastasis.
RESULT: The proportion of M2 macrophages is increased in CRC with liver metastasis compared to those without. Highly metastatic CRC cells release exosomes enriched with miR-106a-5p, which promote macrophages M2 polarization by suppressing SOCS6 and activating JAK2/STAT3 pathway. These M2 macrophages reciprocally enhance CRC liver metastasis. hnRNPA1 regulate the transport of miR-106a-5p into exosomes. Clinically, elevated miR-106a-5p in plasma exosomes correlated with liver metastasis and poor prognosis.
CONCLUSION: CRC-derived exosomal miR-106a-5p plays a critical role in promoting liver metastasis and is a potential biomarker for the prevention and treatment of CRC liver metastasis.

Keywords: Colorectal cancer; Exosomes; Liver metastasis; Macrophage; miRNAs

DOI: https://doi.org/10.1186/s13046-024-03204-7

Exp Cell Res. 2024 Oct 07. pii: S0014-4827(24)00369-0. [Epub ahead of print] 114278

Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories.

Bandar Almutairy, Mohammad S Alzahrani, Dania S Waggas, Hashem O Alsaab.

A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.

Keywords: Cancer; Exosomes; Molecular pathway; exomiRs; gastrointestinal (GI); miRNAs

DOI: https://doi.org/10.1016/j.yexcr.2024.114278

bioRxiv. 2024 Aug 21. pii: 2024.08.20.608894. [Epub ahead of print]

Characterizing the role of exosomal miRNAs in metastasis.

Piyush Agrawal, Gulden Olgun, Arashdeep Singh, Vishaka Gopalan, Idhar Hannenhalli.

Background: Exosomal microRNAs (exomiRs), transported via exosomes, play a pivotal role in intercellular communication. In cancer, exomiRs influence tumor progression by regulating key cellular processes such as proliferation, angiogenesis, and metastasis. Their role in mediating communication between cancer cells and the tumor microenvironment highlights their significance as potential diagnostic and therapeutic targets.
Methodology: In this study, we aimed to characterize the role of exomiRs in influencing the pre-metastatic niche (PMN). Across 7 tumor types, including 4 cell lines and three tumors, we extracted high confidence exomiRs (Log FC >= 2 in exosomes relative to control) and their targets (experimentally identified and targeted by at least 2 exomiRs). Subsequently, we identified enriched pathways and selected the top 100 high-confidence exomiR targets based on the frequency of their appearance in the enriched pathways. These top 100 targets were consistently used throughout the analysis.
Results: Cancer cell line and tumor derived ExomiRs have significantly higher GC content relative to genomic background. Pathway enriched among the top exomiR targets included general cancer-associated processes such as "wound healing" and "regulation of epithelial cell proliferation", as well as cancer-specific processes, such as "regulation of angiogenesis in kidney" (KIRC), "ossification" in lung (LUAD), and "positive regulation of cytokine production" in pancreatic cancer (PAAD). Similarly, 'Pathways in cancer' and 'MicroRNAs in cancer' ranked among the top 10 enriched KEGG pathways in all cancer types. ExomiR targets were not only enriched for cancer-specific tumor suppressor genes (TSG) but are also downregulated in pre-metastatic niche formed in lungs compared to normal lung. Motif analysis shows high similarity among motifs identified from exomiRs across cancer types. Our analysis recapitulates exomiRs associated with M2 macrophage differentiation and chemoresistance such as miR-21 and miR-222-3p, regulating signaling pathways such as PTEN/PI3/Akt, NF-κB, etc. Cox regression indicated that exomiR targets are significantly associated with overall survival of patients in TCGA. Lastly, a Support Vector Machine (SVM) model using exomiR target gene expression classified responders and non-responders to neoadjuvant chemotherapy with an AUROC of 0.96 (in LUAD), higher than other previously reported gene signatures.
Conclusion: Our study characterizes the pivotal role of exomiRs in shaping the PMN in diverse cancers, underscoring their diagnostic and therapeutic potential.

DOI: https://doi.org/10.1101/2024.08.20.608894

J Nanobiotechnology. 2024 Oct 08. 22(1): 610

The new advance of exosome-based liquid biopsy for cancer diagnosis.

Haozhou Tang, Dan Yu, Jiahui Zhang, Maoye Wang, Min Fu, Yu Qian, Xiaoxin Zhang, Runbi Ji, Jianmei Gu, Xu Zhang.

Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use.

Keywords: Biomarker; Cancer; Diagnosis; Exosomes; Liquid biopsy

DOI: https://doi.org/10.1186/s12951-024-02863-0

Clin Chim Acta. 2024 Oct 03. pii: S0009-8981(24)02236-8. [Epub ahead of print]565 119983

Exosomal ncRNAs in liquid biopsies for lung cancer.

Md Sadique Hussain, Gaurav Gupta, Nehmat Ghaboura, Ehssan Moglad, Waleed Hassan Almalki, Sami I Alzarea, Imran Kazmi, Haider Ali, Ronan MacLoughlin, Raimar Loebenberg, Neal M Davies, Sachin Kumar Singh, Kamal Dua.

Exosomal non-coding RNAs (ncRNAs) have become essential contributors to advancing and treating lung cancers (LCs). The development of liquid biopsies that utilize exosomal ncRNAs (exo-ncRNAs) offers an encouraging method for diagnosing, predicting, and treating LC. This thorough overview examines the dual function of exo-ncRNAs as both indicators for early diagnosis and avenues for LC treatment. Exosomes are tiny vesicles secreted by various cells, including cancerous cells, enabling connection between cells by delivering ncRNAs. These ncRNAs, which encompass circular RNAs, long ncRNAs, and microRNAs, participate in the modulation of gene expression and cellular functions. In LC, certain exo-ncRNAs are linked to tumour advancement, spread, and treatment resistance, positioning them as promising non-invasive indicators in liquid biopsies. Additionally, targeting these ncRNAs offers potential for innovative treatment approaches, whether by suppressing harmful ncRNAs or reinstating the activity of tumour-suppressing ones. This review emphasizes recent developments in the extraction and analysis of exo-ncRNAs, their practical applications in LC treatment, and the challenges and prospects for translating these discoveries into clinical usage. Through this detailed examination of the current state of the art, we aim to highlight the significant potential of exo-ncRNAs for LC diagnostics and treatments.

Keywords: Cancer indicators; Diagnosis; Liquid biopsies; Lung cancer; Prognosis; Therapeutic targets

DOI: https://doi.org/10.1016/j.cca.2024.119983