Exosomal Non-Coding RNAs: Diagnostic, Prognostic and Therapeutic Applications in Cancer (original) (raw)
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Exosome-encapsulated ncRNAs: Emerging yin and yang of tumor hallmarks
Frontiers in Genetics, 2022
Tumorigenesis is a multifaceted process, where multiple physiological traits serving as cancer's distinctive characteristics are acquired. "Hallmarks of cancer" is a set of cognitive abilities acquired by human cells that are pivotal to their tumor-forming potential. With limited or no protein-coding ability, noncoding RNAs (ncRNAs) interact with their target molecules and yield significant regulatory effects on several cell cycle processes. They play a "yin" and "yang" role, thereby functioning both as oncogenic and tumor suppressor and considered important in the management of various types of cancer entities. ncRNAs serve as important post-transcriptional and translational regulators of not only unrestricted expansion and metastasis of tumor cells but also of various biological processes, such as genomic mutation, DNA damage, immune escape, and metabolic disorder. Dynamical attributes such as increased proliferative signaling, migration, invasion, and epithelial-mesenchymal transition are considered to be significant determinants of tumor malignancy, metastatic dissemination, and therapeutic resistance. Furthermore, these biological attributes engage tumor cells with immune cells within the tumor microenvironment to promote tumor formation. We elaborate the interaction of ncRNAs with various factors in order to regulate cancer intra/intercellular signaling in a specific tumor microenvironment, which facilitates the cancer cells in acquiring malignant hallmarks. Exosomes represent a means of intercellular communication and participate in the maintenance of the tumor hallmarks, adding depth to the intricate, multifactorial character of malignant neoplasia. To summarize, ncRNAs have a profound impact on tumors, affecting their microcirculation, invasiveness, altered metabolism, microenvironment, and the capacity to modify the host immunological environment. Though the significance of ncRNAs in crosstalk between the tumor and its microenvironment is being extensively explored, we intend to review the hallmarks in the light of exosome-derived non-coding RNAs and their impact on the tumor microenvironment.
Exosomes: New insights into cancer mechanisms
Journal of Cellular Biochemistry, 2019
Exosomes are mobile extracellular vesicles with a diameter 40 to 150 nm. They play a critical role in several processes such as the development of cancers, intercellular signaling, drug resistance mechanisms, and cell‐to‐cell communication by fusion onto the cell membrane of recipient cells. These vesicles contain endogenous proteins and both noncoding and coding RNAs (microRNA and messenger RNAs) that can be delivered to various types of cells. Furthermore, exosomes exist in body fluids such as plasma, cerebrospinal fluid, and urine. Therefore, they could be used as a novel carrier to deliver therapeutic nucleic‐acid drugs for cancer therapy. It was recently documented that, hypoxia promotes exosomes secretion in different tumor types leading to the activation of vascular cells and angiogenesis. Cancer cell‐derived exosomes (CCEs) have been used as prognostic and diagnostic markers in many types of cancers because exosomes are stable at 4°C and −70°C. CCEs have many functional role...
Role of exosomes and exosomal microRNAs in cancer
Future Science OA
A growing body of evidence indicates that exosomes play a critical role in the cell–cell communication process. Exosomes are biological nanoparticles with an average diameter of 30–100 nm in size and are produced by almost all cell types in the human body; however, cancer cells contain higher concentrations of exosomes than healthy cells. They are released into all body fluids and contain double-stranded DNA (originated from nucleus and mitochondria), a variety of RNA species, and specific protein biomarkers that can be utilized as cancer biomarkers and therapeutic targets, and lipids. Therefore, the specific exosomes secreted by tumor cells could be used to predict the existence of the presence of a tumor in cancer patients. This review summarizes the role of exosomes in cancer development and their potential utility in the clinic.
Exosomes and cancer: From oncogenic roles to therapeutic applications
IUBMB Life
Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell-to-cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this
Exosomes: key players in cancer and potential therapeutic strategy
Signal Transduction and Targeted Therapy, 2020
Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.
International journal of oncology, 2015
The role of the extracellular non-coding RNAs, particularly microRNAs present in tumor-derived extravesicles, has been intensively exploited in human cancer as a promising tool for diagnostic and prognostic purposes. Current knowledge on exosomes shows an important role not only as vehicles in the intercellular communication, but the transfer of their content can specifically modulate the surrounding microenvironment, leading to tumor development and progression and affecting therapy response. Based on this, much effort has focused on understanding the mechanisms behind the biology of exosomes and their closely interaction with non-coding RNAs as an efficient tool in tumor diagnostic and therapy. Here we summarize the current knowledge on extracellular and exosomes-enclosed non-coding RNAs, and their importance as potential biomarkers and mediators of intercellular communication in tumor biology.
Tumor cell-derived exosomes: A message in a bottle
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2012
Exosomes constitute the newest mode of intercellular communication, transmitting information between cells. This exchange of molecular information is facilitated by their unique composition which is enriched with enzymes, structural proteins, adhesion molecules, lipid rafts and RNAs. Following the discovery that cancer cells secrete excessive amounts of exosomes compared to normal cells, it became evident that i) these vesicles can be used as diagnostic markers; ii) their active secretion has functional implications, albeit unknown whether they are tumor promoting or suppressing. Notably, the interplay via the exchange of exosomes between cancer cells and between cancer cells and the tumor stroma may promote the transfer of oncogenes (e.g. β-catenin, CEA, HER2, Melan-A/Mart-1 and LMP-1) and onco-microRNAs (e.g. let7, miR1, miR15, miR16 and miR375) from one cell to another, leading to the reprogramming of the recipient cells. The molecular composition and functional role of tumor cell-derived exosomes in tumorigenesis, metastasis and response to therapy are slowly decrypted and the latest findings as well as potential therapeutic strategies are discussed in this review.
MicroRNA-enriched exosome as dazzling dancer between cancer and immune cells
Journal of Physiology and Biochemistry , 2024
x initially noted for the transferrin receptor during reticulocyte maturation, the production of extracellular vesicles (EVs) by cells appears to entail more than merely recycling proteins. Instead, the origin of the EVs, their metabolic status, and the environment in which they reside all influence this process. The incapacity to scan and track exosomes in vivo at a suitable resolution, coupled with present experimental challenges in single-particle detection and separation, continues to hinder EV research. Even with these experimental limitations, fascinating findings have been made. Given that EVs are present in all biological fluids and can perform multicomponent studies, their promise as liquid biopsies is inspiring [6]. Because a unique intracellular regulatory process is involved in the creation of exosomes, which may affect their composition and function(s) once released into the extracellular environment, exosomes are particularly significant in biology [7, 8]. The fact that exosome separation techniques are constantly changing and that current biological markers can only distinguish between a subset of exosomes Extended author information available on the last page of the article Abstract Exosomes are widely recognized for their roles in numerous biological processes and as intercellular communication mediators. Human cancerous and normal cells can both produce massive amounts of exosomes. They are extensively dispersed in tumor-modeling animals' pleural effusions, ascites, and plasma from people with cancer. Tumor cells interact with host cells by releasing exosomes, which allow them to interchange various biological components. Tumor growth, invasion, metastasis, and even tumorigenesis can all be facilitated by this delicate and complex system by modifying the nearby and remote surroundings. Due to the existence of significant levels of biomolecules like microRNA, exosomes can modulate the immune system's stimulation or repression, which in turn controls tumor growth. However, the role of microRNA in exosome-mediated communication between immunological and cancer cells is still poorly understood. This study aims to get the most recent information on the "yin and yang" of exosomal microRNA in the regulation of tumor immunity and immunotherapy, which will aid current cancer treatment and diagnostic techniques.
Cytokine & Growth Factor Reviews
In the last few years cancer research more and more highlighted the importance of cell to cell communication in tumor progression. Among many other functional mechanisms, results evidenced the importance of miRNAs loaded into exosomes and their actions as mediators in intercellular communication, either in the tumor microenvironment or at distant sites. Deregulation of miRNA levels is a prerogative of cancer cells and is reflected in the miRNA cargo of tumor derived exosomes. Thus, learning of circulating miRNA activities add the missing piece we need to understand some unclear aspects of cancer biology. Here we summarized the current knowledge on exosome transfer capabilities between cancer cells and all the cells constituting tumor microenvironment with a particular focus on their miRNA cargos and regulatory functions. The clinical relevance of these molecular aspects is emphasized by numerous cell interactions that ultimately result in normal cell function defeat, relevant to increase tumor malignancy. The quantitative and qualitative evaluation of circulating miRNAs offers new perspective for better diagnosis and prognosis of cancer patients, eventually improving their management. 2. Exosome biogenesis and composition The term exosome (EXO) is referred to small vesicles (40−150 nm)