bims-exocan 2024-12-15 papers

Issue of 2024–12–15
six papers selected by
Muhammad Rizwan, COMSATS University

Pathol Res Pract. 2024 Nov 28. pii: S0344-0338(24)00658-7. [Epub ahead of print]266 155747

Exosomes and tumor virus interlink: A complex side of cancer.

Ibrahim S Topiwala, Aparna Ramachandran, Meghana Shakthi A, Ranjini Sengupta, Rajib Dhar, Arikketh Devi.

Extracellular Vesicles (EVs) based cancer research reveals several complicated sides of cancer. EVs are classified as several subpopulations such as microvesicles, apoptotic bodies, and exosomes. In cancer, exosomes play a significant role as a cellular messenger in tumor development and progression. Tumor-derived exosomes (TEXs) are also a theranostic tool for cancer. Tumor virus-infected cell-derived EVs promote cancer development. Exosomes (a subpopulation of EVs) play a significant role in converting noninfecting cells to infected cells. It transports several biological active cargo (DNA, RNA, protein, and virions) towards the noninfected cells. This cellular transport enhances infection rates via reprogramming of noninfected cells. In this review, we explore tumor viruses, exosomes and tumor viruses interlink, the theranostic landscape of exosomes in tumor virus-associated cancer and the future orientation of exosomes-based virus oncology.

Keywords: Cancer; Exosomes; Extracellular vesicles; Oncogenic virus

DOI: https://doi.org/10.1016/j.prp.2024.155747

Biochem Pharmacol. 2024 Dec 06. pii: S0006-2952(24)00700-7. [Epub ahead of print]232 116699

Exosomes as carriers to stimulate an anti-cancer immune response in immunotherapy and as predictive markers.

Lili Nie, Jingru Ma, Yang Yu, Ying Tao, Zhidu Song, Jian Li.

During this era of rapid advancements in cancer immunotherapy, the application of cell-released small vesicles that activate the immune system is of considerable interest. Exosomes are cell-derived nanovesicles that show great promise for the immunological treatment of cancer because of their immunogenicity and molecular transfer capacity. Recent technological advancements have enabled the identification of functional functions that exosome cargoes perform in controlling immune responses. Exosomes are originated specifically from immune cells and tumor cells and they show unique composition patterns directly related to the immunotherapy against cancer. Exosomes can also deliver their cargo to particular cells, which can affect the phenotypic and immune-regulatory functions of those cells. Exosomes can influence the course of cancer and have therapeutic benefits by taking part in several cellular processes; as a result, they have the dual properties of activating and restraining cancer. Exosomes have tremendous potential for cancer immunotherapy; they may develop into the most powerful cancer vaccines and carriers of targeted antigens and drugs. Comprehending the potential applications of exosomes in immune therapy is significant for regulating cancer progression. This review offers an analysis of the function of exosomes in immunotherapy, specifically as carriers that function as diagnostic indicators for immunological activation and trigger an anti-cancer immune response. Moreover, it summarizes the fundamental mechanism and possible therapeutic applications of exosome-based immunotherapy for human cancer.

Keywords: Cancer immunotherapy; Exosomes; Immune activation; Immune cell-derived exosomes; Nanovesicles; Tumor-derived exosomes

DOI: https://doi.org/10.1016/j.bcp.2024.116699

Front Oncol. 2024 ;14 1440996

Gastric cancer cell-derived exosomal miRNA-128-3p promotes angiogenesis by targeting SASH1.

Hao Yan, Xinyu Cai, Jianna Zhang, Hongpeng Zhao, Hongwen Wu, Jingbo Zhang, Lanzhi Xu, Shizheng Liu, Yuanwei Zang, Shanshan Fu.

Exosomes, key components of the tumour microenvironment, can mediate intercellular communication through the delivery of various signalling molecules, including microribonucleic acids (miRNAs), and ultimately participate in regulating the process of tumour development. In this study, we aimed to investigate the reason and mechanism by which exosomal miRNAs derived from gastric cancer cells affect carcinogenesis and metastasis. Among these miRNAs, microRNA-128-3p (miR-128-3p) was highly expressed in serum exosomes isolated from gastric cancer patients, as confirmed by high-throughput sequencing and subsequent experiments. Coculture of gastric cancer-derived exosomes overexpressing miR-128-3p with human umbilical vein endothelial cells (HUVECs) significantly enhanced HUVEC proliferation, migratio n and angiogenesis. Bioinformatics analysis suggested SASH1 as the target gene of miR-128-3p. The dual luciferase assay and Western blot analysis results confirmed that miR-128-3p directly targeted SASH1 to inhibit its expression in HUVECs. Therefore, this study provides preliminary evidence that gastric cancer-derived exosomal miR-128-3p promotes tumour angiogenesis by targeting SASH1, reveals the potential diagnostic and therapeutic value of cancer-derived exosomal miR-128-3p, and provides new insights into the novel molecular mechanisms regulating metastasis. This study provides further information for understanding the role of gastric cancer-derived exosomal miR-128-3p in cancer progression and to discover new therapeutic targets.

Keywords: angiogenesis; exosome; gastric cancer; miR-128-3p; targeted therapy

DOI: https://doi.org/10.3389/fonc.2024.1440996

J Reprod Immunol. 2024 Dec 03. pii: S0165-0378(24)00212-2. [Epub ahead of print]167 104403

Exosome's role in ovarian disease pathogenesis and therapy; Focus on ovarian cancer and failure.

Hashem O Alsaab, Bandar Almutairy, Ali Othman Almobarki, Miad A Abu Mughaedh, Mohammad S Alzahrani.

In the eukaryotic system, exosomes are categorized as unique extracellular vesicles with dimensions ranging from 30 to 150 nm. These vesicles contain a variety of endogenous molecules, such as proteins, DNA, mRNA, microRNA, and circular RNA. They are essential for a wide range of metabolic events and have the potential to be used as therapeutic or diagnostic targets for a number of diseases, including ovarian diseases. By inducing changes in the surrounding environment, the donor exosomes transfer their contents to the receiving cells, so demonstrating the biological implications of major interactions between cells. Mesenchymal stem cells (MSCs) have produced exosomes have shown promise as a treatment for premature organ failure (POF or POI). Furthermore, exosomal transport has many complexities, and contributes to the pathophysiology of ovarian cancer by affecting cell growth, migration, metastastsis and etc. Owing to these facts, in this paper, we present the progress developed in the understanding of exosomes as a viable therapeutic avenue and indisputable prognostic targets in ovarian disorders.

Keywords: Cancer; Exosome; Microenvironment; Ovarian; POF

DOI: https://doi.org/10.1016/j.jri.2024.104403

Cancer Sci. 2024 Dec 10.

Tumor exosomal RNPEP promotes lung metastasis of liver cancer via inducing cancer-associated fibroblast activation.

Yuankun Chen, Gaofeng Pan, Yijun Yang, Haifeng Wu, Minhua Weng, Qiuping Wu, Yufeng Gao, Wenting Li.

Cancer-associated fibroblasts (CAFs) are essential players in the tumor microenvironment (TME) due to their roles in facilitating tumor progression and metastasis. It is worth noting that the high-metastatic hepatocellular carcinoma (HCC) cell-derived exosomes have exhibited the ability to transform normal fibroblasts into CAFs, which further fosters the lung metastasis of low-metastatic HCC cells. Yet, the mechanisms underlying this tumor exosome-induced metastatic niche formation are poorly explored. In this study, the secreted protein arginyl aminopeptidase (RNPEP) was highly expressed in the plasma of patients with HCC. In addition, high-metastatic HCC cells showed augmented RNPEP expression levels in their exosomes. These exosomes induced obvious CAF-like properties in the human fibroblast cell line MRC-5, as evidenced by the increased CAF marker expression, and enhanced migratory ability. More strikingly, the secretions from high-metastatic tumor exosome-educated MRC-5 cells increased tumor stemness and promoted epithelial-mesenchymal transition (EMT) in MHCC-97L cells, a low-metastatic HCC cell line. However, the knockdown of RNPEP in exosomes from high-metastatic HCC cells abated the changes described above. Animal studies in vivo highlighted the pro-tumor and pro-metastatic effects of exosomal RNPEP on MHCC-97L cells by inducing CAF activation. Furthermore, tumor-derived exosomal RNPEP induced the activation of NF-κB signaling in MRC-5 cells, a critical pathway associated with CAF activation. Collectively, these results provide novel insight into tumor-derived exosomal RNPEP for its crosstalk with CAFs during HCC lung metastasis.

Keywords: RNPEP; cancer‐associated fibroblast activation; exosome; hepatocellular carcinoma (HCC); lung metastasis

DOI: https://doi.org/10.1111/cas.16417

Gene. 2024 Dec 04. pii: S0378-1119(24)01022-9. [Epub ahead of print]937 149141

The significance of exosomal non-coding RNAs (ncRNAs) in the metastasis of colorectal cancer and development of therapy resistance.

Omid Rahbar Farzam, Sahand Eslami, Ali Jafarizadeh, Sania Ghobadi Alamdari, Reza Dabbaghipour, Shima Alizadeh Nobari, Behzad Baradaran.

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.

Keywords: Bioinformatics; Colorectal cancer; Drug resistance; Exosome; Metastasis; non-coding RNAs

DOI: https://doi.org/10.1016/j.gene.2024.149141