mRNA-based therapeutics: powerful and versatile tools to combat diseases

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

Published: May 21, 2022

Abstract The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range incurable diseases. Recent rapid advances in biotechnology and molecular medicine have enabled the production almost any functional protein/peptide human body by introducing mRNA as vaccine or agent. This represents rising precision field with promise for preventing treating many intractable genetic In addition, vitro transcribed achieved programmed production, which is more effective, faster design well flexible cost-effective than conventional approaches that may offer. Based on these extraordinary advantages, vaccines characteristics swiftest response large-scale outbreaks infectious diseases, such currently devastating pandemic COVID-19. It always been scientists’ desire improve stability, immunogenicity, translation efficiency, delivery system achieve efficient safe mRNA. Excitingly, scientific dreams gradually realized rapid, amazing achievements biology, technology, vaccinology, nanotechnology. this review, we comprehensively describe mRNA-based therapeutics, including their principles, manufacture, application, effects, shortcomings. We also highlight importance optimization systems successful therapeutics discuss key challenges opportunities developing tools into powerful versatile genetic, infectious, cancer, other refractory

Language: Английский

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Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

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

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Specific expression and functions of circular RNAs

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(3), P. 481 - 491

Published: Feb. 15, 2022

Language: Английский

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N6-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating β-catenin signaling

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Nov. 23, 2020

Abstract Background and aims Accumulating evidence suggests that the primary acquired resistance of hepatocellular carcinoma (HCC) to sorafenib is mediated by multiple molecular, cellular, microenvironmental mechanisms. Understanding these mechanisms will enhance likelihood effective therapy. Methods In vitro in vivo experiments were performed clinical samples online databases for investigation. Results this study, we found a circular RNA, circRNA-SORE, which up-regulated so rafenib-resistant HCC cells, was necessary maintenance resistance, silencing circRNA-SORE substantially increased efficacy sorafenib-induced apoptosis. Mechanistic studies determined sequestered miR-103a-2-5p miR-660-3p acting as microRNA sponge, thereby competitively activating Wnt/β-catenin pathway inducing resistance. The level sorafenib-resistant cells resulted from RNA stability. This caused an N 6 -methyladenosine (m A) at specific adenosine circRNA-SORE. delivery interfering local short hairpin lentivirus injection enhanced animal models. Conclusions work indicates novel mechanism maintaining proof-of-concept study targeting sorafenib-treated patients pharmaceutical intervention advanced HCC.

Language: Английский

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Emerging Role of Circular RNAs in Hepatocellular Carcinoma Immunotherapy

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

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Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 1, 2024

Abstract Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor has a significant impact on mortality rates. Nevertheless, swift advancement of contemporary technology not seamlessly aligned with evolution detection methodologies, resulting in deficit innovative efficient clinical assays for GIC. Given that exosomes are preferentially released by myriad cellular entities, predominantly originating from neoplastic cells, this confers composition enriched cancer-specific constituents. Furthermore, exhibit ubiquitous presence across diverse biological fluids, endowing them inherent advantages non-invasiveness, real-time monitoring, specificity. The unparalleled render as an ideal liquid biopsy biomarker early diagnosis, prognosticating potential development GIC metastasis. In review, we summarized latest research progress possible targets cancer-derived (CDEs) emphasis mechanisms exosome promoting metastasis, highlighting roles CDEs treatment

Language: Английский

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Circular RNAs in cancer: Limitations in functional studies and diagnostic potential

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 75, P. 49 - 61

Published: Oct. 6, 2020

Circular RNAs (circRNAs) are a large class of noncoding RNAs, generated from process called back-splicing, that possess critical regulatory functions in many cellular events. A body literature has reported various circRNA and their underlying mechanisms, including sponging miRNA, exerting transcriptional translational regulation, interacting with proteins, translating into peptides proteins. CircRNA dysregulation been implicated cancers, lung, breast, liver, gastric, colorectal, ovarian cancer. They detectable bodily fluids relatively stable, making them potential cancer biomarker candidates. Furthermore, targeting expression levels is therapeutic approach for treating cancers. In this review, we describe the functional mechanisms circRNAs discuss limitations current mechanism studies. Following this, outline to be effective biomarkers cancers present circRNA-based approaches. Finally, challenges using as diagnostic tools propose future research directions.

Language: Английский

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Emerging Roles of Exosomal Circular RNAs in Cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Oct. 8, 2020

Circular RNA (circRNA) is a type of noncoding that forms covalently closed continuous loop. The expression pattern circRNA varies among cell types and tissues, many circRNAs are aberrantly expressed in various cancers. Aberrantly have been shown to play crucial roles carcinogenesis, functioning as microRNA sponges or new templates for protein translation. Recent research has enriched exosomes. Exosomes secretory vesicles mediate intercellular communication through the delivery cargo, including proteins, lipids, DNA, RNA. Exosome-mediated crosstalk between cancer cells tumor microenvironment promotes epithelial-mesenchymal transition, angiogenesis, immune escape, thus may contribute invasion metastasis. In this review, we discuss biological functions exosomal their significance progression. Additionally, potential clinical applications biomarkers therapy.

Language: Английский

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Circular RNA hsa_circ_0004277 Stimulates Malignant Phenotype of Hepatocellular Carcinoma and Epithelial-Mesenchymal Transition of Peripheral Cells

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 8

Published: Jan. 12, 2021

Accumulating evidence shows that exosomal circRNAs reflect the physiological status of donor cells, and various cell reactions are induced after captured by recipient cells. In this study, qRT-PCR was performed to detect circ-0004277 expression in hepatocellular carcinoma (HCC) lines, tissues, plasma exosomes. The effects on proliferation migration HCC cells were assessed counting, 5-ethynyl-2′-deoxyuridine assays, Transwell tumor formation nude mice. We found significantly upregulated exosomes compared normal controls. Overexpression enhanced proliferation, migration, epithelial-mesenchymal transition (EMT) vivo vitro . Furthermore, from surrounding stimulated EMT progression. ZO-1, a tight junction adapter protein, downregulated tissues. conclusion, our findings suggest promotes malignant phenotype via inhibition ZO-1 promotion addition, stimulates peripheral through cellular communication further promote invasion into

Language: Английский

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Circular RNA FAT atypical cadherin 1 (circFAT1)/microRNA-525-5p/spindle and kinetochore-associated complex subunit 1 (SKA1) axis regulates oxaliplatin resistance in breast cancer by activating the notch and Wnt signaling pathway

Bioengineered, Journal Year: 2021, Volume and Issue: 12(1), P. 4032 - 4043

Published: Jan. 1, 2021

Increasing evidence has confirmed the vital roles of circular RNAs (CircRNAs) in drug resistance breast cancer (BC). Herein, we intended to study effect RNA FAT atypical cadherin 1 (circFAT1) on BC oxaliplatin (OX) and find out potential molecular mechanism it. In this study, mRNA protein levels genes were measured by RT-qPCR western blotting, respectively. Luciferase reporter assay relationship between microRNA-525-5p (miR-525-5p) circFAT1 or spindle kinetochore-associated complex subunit (SKA1). CCK-8, transwell, flow cytometry experiments utilized investigate chemosensitivity, migration, invasion, apoptosis cells. Gene Set Enrichment Analysis (GSEA) was applied discover possible pathways related SKA1. It uncovered that overexpressed OX-resistant tissues Functional showed depletion reduced level chemoresistance-related genes. Moreover, knockdown remarkably facilitated decreased OX (half-maximal inhibitory concentration) IC50 value, invasion identified miR-525-5p directly targeted Besides, rescue assays exhibited promoted cells via miR-525-5p/SKA1 regulatory network. Furthermore, GSEA blotting SKA1 activated Notch Wnt pathway conclusion, our results demonstrated conferred regulating pathway, providing a therapeutic target for patients with BC.

Language: Английский

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