Gastrointestinal cancer drug resistance: the role of exosomal miRNAs

Salehi, Mahsa; Vafadar, Asma; Khatami, Seyyed Hossein; Taheri‐Anganeh, Mortaza; Vakili, Omid; Savardashtaki, Amir; Negahdari, Babak; Naeli, Parisa; Behrouj, Hamid; Ghasemi, Hassan; Movahedpour, Ahmad

doi:10.1007/s11033-021-07007-3

Cited by 16 publications

(8 citation statements)

References 85 publications

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“…Despite the fact that the precise mechanisms underlying drug resistance are still incompletely understood, a number of contributing factors have been identified. Exosomes have been linked to targeting GI cancer invasion, angiogenesis, and treatment resistance [ 102 – 104 ]. Thus, exosomes can mediate endocytosis of specific medications into cancer cells [ 58 ], and can be genetically modified to express peptides or ligands on their surface to facilitate this process.…”

Section: Exosomes As Biological Drug Carriersmentioning

confidence: 99%

Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research

Shojaeian,

Naeimi Torshizi,

Parsapasand

et al. 2024

Discov Onc

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Exosomes are small extracellular vesicles (30–150 nm) that are formed by endocytosis containing complex RNA as well as protein structures and are vital in intercellular communication and can be used in gene therapy and drug delivery. According to the cell sources of origin and the environmental conditions they are exposed to, these nanovesicles are very heterogeneous and dynamic in terms of content (cargo), size and membrane composition. Exosomes are released under physiological and pathological conditions and influence the pathogenesis of cancers through various mechanisms, including angiogenesis, metastasis, immune dysregulation, drug resistance, and tumor growth/development. Gastrointestinal cancer is one of the deadliest types of cancer in humans and can involve organs e.g., the esophagus and stomach, or others such as the liver, pancreas, small intestine, and colon. Early diagnosis is very important in this field because the overall survival of patients is low due to diagnosis in late stages and recurrence. Also, various therapeutic strategies have failed and there is an unmet need for the new therapeutic agents. Exosomes can become promising candidates in gastrointestinal cancers as biomarkers and therapeutic agents due to their lower immunity and passing the main physiological barriers. In this work, we provide a general overview of exosomes, their biogenesis and biological functions. In addition, we discuss the potential of exosomes to serve as biomarkers, agents in cancer treatment, drug delivery systems, and effective vaccines in immunotherapy, with an emphasis on gastrointestinal cancers. Graphical Abstract

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Section: Exosomes As Biological Drug Carriersmentioning

confidence: 99%

Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research

Shojaeian,

Naeimi Torshizi,

Parsapasand

et al. 2024

Discov Onc

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“…Several mechanisms modulated by miRNAs have been recognized in relation to BC chemoresistance; targeting genes involved in drug efflux and metabolism; cellular responses to chemotherapeutics (e.g., apoptosis, cell cycle arrest, and DNA repair); epigenetic alterations (e.g., DNA methylation and histone modifications); and deregulation of drug targets and receptors, which are the best examples in the field ( Kutanzi et al, 2011 ). On the other hand, the miRNA-containing exosomes secreted by tumor cells can possibly be internalized by other cells to deliver gene modulatory characteristics to the recipient cells ( Bach et al, 2017 ; Schwarzenbach, 2017 ; Salehi et al, 2022 ). As an example, it has been demonstrated that endothelial cell-derived exosomal miR-503, which is increased after neoadjuvant chemotherapy, can impair tumor growth, invasion, and proliferation in BC by inhibiting the expression of cyclin D2- and D3-encoding genes (CCND2 and CCND3) ( Bovy et al, 2015 ).…”

Section: Molecular Mechanisms By Which Exosomal Ncrnas Interfere With...mentioning

confidence: 99%

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

et al. 2023

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Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

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“…Exosomes are small vesicles with a diameter of 40 to 150 nm. They are derived from the cell membrane and act as key regulators in cell–cell communication [ 20 , 21 ]. First reports of exosomes in extracellular spaces were made during the late 1980s [ 22 ].…”

Section: Exosome Biogenesismentioning

confidence: 99%

Recent advances in the roles of exosomal microRNAs (exomiRs) in hematologic neoplasms: pathogenesis, diagnosis, and treatment

2023

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In clinical diagnosis, the capability of exosomes to serve as biomarkers is one of the most important biological functions of exosomes. The superior stability of exosome biomarkers makes them superior to those isolated from traditional samples such as serum and urine. Almost all body fluids contain exosomes, which contain proteins, nucleic acids, and lipids. Several molecular components of exosomes, including exosome proteins and microRNAs (miRNAs), are promising diagnostic biomarkers. These exosomes may carry genetic information by containing messenger RNA (mRNA) and miRNA. The miRNAs are small noncoding RNAs that regulate protein-coding genes by acting as translational repressors. It has been shown that miRNAs are mis-expressed in a range of conditions, including hematologic neoplasms. Additionally, miRNAs found within exosomes have been linked with specific diseases, including hematologic neoplasms. Numerous studies suggest that circulating exosomes contain miRNAs similar to those found in parental cancer cells. Exosomes contain miRNAs that are released by almost all kinds of cells. MiRNAs are packaged into exosomes and delivered to recipient cells, and manipulate its function. It has been recognized that exosomes are new therapeutic targets for immunotherapy and biomedicine of cancers. The current review discusses the current evidence around exosomal miRNAs involved in the pathogenesis, diagnosis, and treatment of hematologic neoplasms.

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Gastrointestinal cancer drug resistance: the role of exosomal miRNAs

Cited by 16 publications

References 85 publications

Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research

Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

Recent advances in the roles of exosomal microRNAs (exomiRs) in hematologic neoplasms: pathogenesis, diagnosis, and treatment

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