Emerging Role of Circular RNAs in Hepatocellular Carcinoma Immunotherapy DOI Open Access
Tasneem Abaza, Mostafa K. Abd El‐Aziz,

Kerolos Ashraf Daniel

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16484 - 16484

Published: Nov. 18, 2023

Hepatocellular carcinoma (HCC) is a highly fatal malignancy with limited therapeutic options and high recurrence rates. Recently, immunotherapeutic agents such as immune checkpoint inhibitors (ICIs) have emerged new paradigm shift in oncology. ICIs, programmed cell death protein 1 (PD-1) inhibitors, provided source of hope for patients advanced HCC. Yet, the eligibility criteria HCC ICIs are still missing piece puzzle. Circular RNAs (circRNAs) recently class non-coding that play fundamental role cancer pathogenesis. Structurally, circRNAs resistant to exonucleolytic degradation longer half-life than their linear counterparts. Functionally, possess capability influence various facets tumor microenvironment, especially at tumor–immune synapse. Notably, been observed control expression molecules within cells, potentially impeding effectiveness ICIs. Therefore, this renders them potential cancer-immune biomarkers diagnosis, prognosis, regimen determinants. In review, authors shed light on structure functional roles and, most importantly, highlight promising immunomodulation

Language: Английский

Isolation and characterization of exosomes for cancer research DOI Creative Commons
Le Zhu, Haoting Sun, Shun Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Nov. 10, 2020

Abstract Exosomes are a subset of extracellular vesicles that carry specific combinations proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests exosomes participate in intercellular communication act as important molecular vehicles the regulation numerous physiological pathological processes, including cancer development. released by various cell types under both normal conditions, they can be found multiple bodily fluids. Moreover, carrying wide variety macromolecules provide window into altered cellular or tissue states. Their presence biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers diagnosis, prediction, surveillance. Due to their biocompatibility low immunogenicity cytotoxicity, have clinical applications development innovative therapeutic approaches. Here, we summarize recent advances technologies exosome isolation research. We outline functions regulating tumor metastasis, drug resistance, immune modulation context Finally, discuss prospects challenges exosome-based therapeutics.

Language: Английский

Citations

363

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases DOI Creative Commons
Chen Li, Yu‐Qing Ni, Hui Xu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 10, 2021

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), are closely related variety biological functional aspects human health. When the exosomal ncRNAs undergo tissue-specific changes due diverse internal or external disorders, they can cause tissue dysfunction, aging, diseases. In this review, we comprehensively discuss underlying regulatory mechanisms exosomes in addition, explore current knowledge on roles miRNAs, lncRNAs, circRNAs health diseases, including cancers, metabolic neurodegenerative cardiovascular autoimmune infectious determine their potential implication biomarker identification therapeutic exploration.

Language: Английский

Citations

274

Targeting non-coding RNAs to overcome cancer therapy resistance DOI Creative Commons
Baoqing Chen, Mihnea P. Dragomir, Yang Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 13, 2022

Abstract It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), widely appreciated as pervasive regulators of multiple cancer hallmarks such proliferation, apoptosis, invasion, metastasis, genomic instability. Despite recent discoveries in therapy, resistance to chemotherapy, radiotherapy, targeted immunotherapy continue be a major setback. Recent studies have shown ncRNAs also play role different therapies by rewiring essential signaling pathways. In this review, we present intricate mechanisms through which dysregulated control four types therapies. We will focus on current clinical implications biomarkers predict treatment response (intrinsic resistance) detect therapy after start (acquired resistance). Furthermore, potential targeting ncRNA overcome resistance, discuss challenges ncRNA-targeted therapy—especially development delivery systems.

Language: Английский

Citations

258

Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment DOI Creative Commons

Zijie Xu,

Yi Chen, Ling Ma

et al.

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(10), P. 3133 - 3154

Published: April 9, 2022

Exosomes have a crucial role in intercellular communication and mediate interactions between tumor cells tumor-associated macrophages (TAMs). Exosome-encapsulated non-coding RNAs (ncRNAs) are involved various physiological processes. Tumor-derived exosomal ncRNAs induce M2 macrophage polarization through signaling pathway activation, signal transduction, transcriptional post-transcriptional regulation. Conversely, TAM-derived promote proliferation, metastasis, angiogenesis, chemoresistance, immunosuppression. MicroRNAs gene silencing by directly targeting mRNAs, whereas lncRNAs circRNAs act as miRNA sponges to indirectly regulate protein expressions. The of tumor-host is ubiquitous. Current research increasingly focused on the microenvironment. On basis "cancer-immunity cycle" hypothesis, we discuss effects immune T cell exhaustion, overexpression programmed death ligands, create immunosuppressive Furthermore, potential applications prospects clinical biomarkers drug delivery systems. 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Language: Английский

Citations

205

Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential DOI Creative Commons
Zhengjun Lin, Yanlin Wu, Yiting Xu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 13, 2022

Abstract Mesenchymal stem cells (MSCs) are multipotent stromal that can be obtained from various human tissues and organs. They differentiate into a wide range of cell types, including osteoblasts, adipocytes chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated MSCs play critical roles cancer biology. The crosstalk between tumour has been found to regulate many behaviours, such as proliferation, metastasis epithelial-mesenchymal transition (EMT). Multiple lines evidence demonstrated secrete exosomes modulate the microenvironment important development. Notably, very recent works shown mesenchymal cell-derived (MSC-derived exosomes) critically involved resistance chemotherapy agents, targeted-therapy drugs, radiotherapy immunotherapy. In this review, we systematically summarized emerging detailed molecular mechanisms MSC-derived mediating therapy resistance, providing novel insights clinical applications management.

Language: Английский

Citations

184

Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma DOI Creative Commons
Zongqiang Hu, Gang Chen,

Yingpeng Zhao

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 18, 2023

Abstract Background Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety tumors. Dysfunction CD8 + T cells is main factor immune escape from hepatocellular carcinoma (HCC). Nevertheless, effect exosome-derived circRNAs on T-cell dysfunction needs further exploration. Methods The circCCAR1 tumorigenesis and metastasis HCC was assessed by vitro vivo functional experiments. function measured enzyme-linked immunosorbent assay (ELISA), western blotting flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, MS2 pull-down assays were used exploration mechanism. A mouse model with reconstituted human system components (huNSG mice) constructed explore role exosomal resistance anti-PD1 therapy HCC. Results Increased levels existed tumor tissues plasma patients, culture supernatant cells. CircCCAR1 accelerated growth vivo. E1A binding protein p300 (EP300) eukaryotic translation initiation 4A3 (EIF4A3) promoted biogenesis circCCAR1, Wilms 1-associated (WTAP)-mediated m6A modification enhanced stability insulin-like 2 mRNA-binding 3 (IGF2BP3). acted as sponge for miR-127-5p upregulate its target WTAP feedback loop comprising circCCAR1/miR-127-5p/WTAP axis formed. secreted heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal taken caused stabilizing PD-1 protein. immunotherapy. Furthermore, increased cell division cycle apoptosis regulator 1 (CCAR1) induced EP300 CCAR1 β-catenin protein, which transcription PD-L1. Conclusions enhances released contributes immunosuppression facilitating induces immunotherapy, providing potential therapeutic strategy patients.

Language: Английский

Citations

180

Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC DOI Creative Commons
Shiwei Chen, Shu‐Qiang Zhu, Xu Pei

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Nov. 9, 2021

CD8+ T cells play a critical role in the innate antitumour immune response. Recently, cell dysfunction has been verified various malignant cancers, including non-small lung cancer (NSCLC). However, molecular biological mechanisms of human NSCLC are still unclear.The expression circular ubiquitin-specific protease-7 (circUSP7) tissues, exosomes, and lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from culture medium plasma patients using an ultracentrifugation method ExoQuick Exosome Precipitation Solution kit. The exosomes then characterized transmission electronic microscopy (TEM), NanoSight western blotting. circUSP7 assessed enzyme-linked immunosorbent assay (ELISA). In vivo RNA (circRNA) precipitation (circRIP), immunoprecipitation (RIP), luciferase reporter assays performed to explore cells. retrospective study, clinical characteristics prognostic significance tissues determined.The levels higher than matched adjacent nontumour tissues. Increased indicate poor prognosis with NSCLC. found patient is predominantly secreted exosomal manner, inhibits IFN-γ, TNF-α, Granzyme-B Perforin secretion Furthermore, function upregulating Src homology region 2 (SH2)-containing protein tyrosine phosphatase (SHP2) via sponging miR-934. Finally, we show that may promote resistance anti-PD1 immunotherapy patients.Exosomal contributes immunosuppression promoting CircUSP7 induces immunotherapy, providing potential therapeutic strategy for patients.

Language: Английский

Citations

174

Exosomes as mediators of immune regulation and immunotherapy in cancer DOI
Fernanda G. Kugeratski, Raghu Kalluri

FEBS Journal, Journal Year: 2020, Volume and Issue: 288(1), P. 10 - 35

Published: Sept. 28, 2020

Exosomes are nanosized extracellular vesicles of endosomal origin that enclose a multitude functional biomolecules. have emerged as key players intercellular communication in physiological and pathological conditions. In cancer, depending on the context, exosomes can oppose or potentiate development an aggressive tumor microenvironment, thereby impacting progression clinical outcome. Increasing evidence has established important mediators immune regulation they deliver plethora signals either support restrain immunosuppression lymphoid myeloid cell populations tumors. Here, we review current knowledge related to exosome-mediated (T lymphocytes, B NK cells) (macrophages, dendritic cells, monocytes, myeloid-derived suppressor neutrophils) cancer. We also discuss translational potential engineered immunomodulatory agents for cancer therapy.

Language: Английский

Citations

158

Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets DOI Creative Commons

Jing Yang,

Jin Xu, Wei Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

Citations

152

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases DOI Creative Commons
Guoxia Wen, Tong Zhou, Wanjun Gu

et al.

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(12), P. 911 - 946

Published: Nov. 1, 2020

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with closed loop structure. The majority circRNAs are formed by back-splicing process in pre-mRNA splicing. Their expression dynamically regulated and shows spatiotemporal patterns among cell types, tissues developmental stages. CircRNAs have important biological functions many physiological processes, their aberrant implicated human diseases. Due to high stability, becoming promising biomarkers diseases, such as cardiovascular autoimmune diseases cancers. In this review, we focus on the translational potential using blood liquid biopsy for We highlight abundant expression, essential significant correlations various components peripheral blood, including whole cells extracellular vesicles. addition, summarize current knowledge circRNA disease diagnosis or prognosis.

Language: Английский

Citations

143