Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 17, 2022

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with potential effectively extend patient survival. However, development drug resistance seriously limits clinical efficiency ultimately results in treatment failure death. A large number studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long RNAs, circular are widely involved regulation resistance. Their dysregulation contributes by modulating expression specific target genes cellular apoptosis, autophagy, efflux, epithelial-to-mesenchymal transition (EMT), stem cells (CSCs). Moreover, some ncRNAs also possess great as efficient, biomarkers diagnosis prognosis well targets patients. In this review, we summarize recent findings on emerging role underlying mechanisms focus their applications treatment. This information will be benefit early prognostic assessments ncRNA-based strategies

Language: Английский

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Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1

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

Published: July 17, 2023

Abstract Background Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to progression OS, but its potential molecular regulatory role still unclear. Based on ability couple exosomes for targeted delivery signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers OS. Methods We identified ferroptosis-related miRNAs and messenger acids(mRNAs) using bioinformatics analysis performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, used RT-qPCR IHC verify level miR-144-3p ZEB1. Stable gene cell lines were fabricated vitro experiments. Cell viability, migration invasion determined by CCK-8 transwell experiment. Use corresponding reagent kit detect GSH/GSSG ratio, Fe 2+ level, MDA ROS measure GPX4, ACSL4 xCT WB. also constructed nude mice model vivo Finally, stability miRNA/mRNA axis was verified functional rescue Results Low ZEB1 tissues observed. Overexpression promote ferroptosis, reduce cells, prevent In addition, overexpression downregulate mice. Knockdown has opposite effect. experiment validated regulate downstream ZEB1, participates occurrence development interfering redox homeostasis metabolism. Conclusions MiR-144-3p induce negatively regulating thereby inhibiting proliferation, migration, cells. Graphical

Language: Английский

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

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

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Non-coding RNAs regulating mitochondrial function in cardiovascular diseases

Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 101(5), P. 501 - 526

Published: April 4, 2023

Language: Английский

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Non-coding RNA-mediated modulation of ferroptosis in cardiovascular diseases

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114993 - 114993

Published: June 9, 2023

Cardiovascular disease (CVD) is a major contributor to increasing morbidity and mortality worldwide seriously threatens human health life. Cardiomyocyte death considered the pathological basis of various CVDs, including myocardial infarction, heart failure, aortic dissection. Multiple mechanisms, such as ferroptosis, necrosis, apoptosis, contribute cardiomyocyte death. Among them, ferroptosis an iron-dependent form programmed cell that plays vital role in physiological processes, from development aging immunity CVD. The dysregulation has been shown be closely associated with CVD progression, yet its underlying mechanisms are still not fully understood. In recent years, growing amount evidence suggests non-coding RNAs (ncRNAs), particularly microRNAs, long RNAs, circular involved regulation thus affecting progression. Some ncRNAs also exhibit potential value biomarker and/or therapeutic target for patients this review, we systematically summarize findings on their We focus clinical applications diagnostic prognostic biomarkers well targets treatment. DATA AVAILABILITY: No new data were created or analyzed study. Data sharing applicable article.

Language: Английский

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Microplastics induced inflammation and apoptosis via ferroptosis and the NF-κB pathway in carp

Aquatic Toxicology, Journal Year: 2023, Volume and Issue: 262, P. 106659 - 106659

Published: Aug. 14, 2023

Language: Английский

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Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 8, 2023

Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation pathological mechanisms, low efficiency detection assessment methods, lack individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular (circRNA), endogenous regulators that widely involved in modulation almost all aspects life activities, from organogenesis aging immunity cancer. They commonly play vital roles various biological processes by regulating gene expression via their interactions DNA, RNA, or protein. An increasing amount studies have demonstrated ncRNAs closely correlated initiation development LC. Their dysregulation promotes progression distinct such as influencing protein activity, activating oncogenic signaling pathways, altering specific expression. Furthermore, some present certain values biomarker candidates targets for patients. A complete understanding mechanisms may be highly beneficial developing ncRNA-based therapeutics This review mainly focuses on intricate miRNA, lncRNA, circRNA discuss underlying applications treatment.

Language: Английский

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Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 1, 2024

Abstract Lung cancer stands as the most prevalent form of globally, posing a significant threat to human well-being. Due lack effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still potential means eradicating cancer, usually miss best chance for treatment, even after may experience tumor recurrence. Additionally, chemotherapy, mainstay treatment has be chemo-resistant, resulting in poor clinical outcomes. The emergence liquid biopsies garnered considerable attention owing their noninvasive nature ability continuous sampling. Technological advancements have propelled circulating cells (CTCs), DNA (ctDNA), extracellular vesicles (EVs), metabolites, tumor-educated platelets (TEPs), tumor-associated antigens (TAA) forefront key biopsy biomarkers, demonstrating intriguing encouraging results diagnosis prognostic evaluation This review provides an overview molecular biomarkers assays utilized encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, TAAs TEPs. Furthermore, we expound on practical applications biopsies, including diagnosis, response monitoring, evaluation, recurrence monitoring context

Language: Английский

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Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 10, 2024

Abstract Ferroptosis is a newly identified iron-dependent form of death that becoming increasingly recognized as promising avenue for cancer therapy. N6-methyladenosine (m 6 A) the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, crucial role m A regulating ferroptosis during colorectal (CRC) tumorigenesis remains elusive. Herein, we find increased ferroptotic cell and correlates with decreased demethylase fat mass obesity-associated protein (FTO) expression. Functionally, demonstrate suppressing FTO significantly induces CRC death, well enhancing sensitivity inducer (Erastin RSL3) treatment. Mechanistically, high expression solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions an A-YTHDF2 dependent manner, thereby counteracting stress. In addition, identify Mupirocin novel inhibitor FTO, inhibits tumor growth. Clinically, levels SLC7A11, GPX4, are highly correlated tissues. Our findings reveal protects from promoting through triggering SLC7A11/GPX4

Language: Английский

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Ferroptosis, necroptosis, and pyroptosis in the occurrence and development of ovarian cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 25, 2022

Ovarian cancer (OC) is one of the most common malignancies that causes death in women and a heterogeneous disease with complex molecular genetic changes. Because relatively high recurrence rate OC, it crucial to understand associated mechanisms drug resistance discover potential target for rational targeted therapy. Cell genetically determined process. Active orderly cell prevalent during development living organisms plays critical role regulating life homeostasis. Ferroptosis, novel type discovered recent years, distinct from apoptosis necrosis mainly caused by imbalance between production degradation intracellular lipid reactive oxygen species triggered increased iron content. Necroptosis regulated non-cysteine protease–dependent programmed necrosis, morphologically exhibiting same features as occurring via unique mechanism different apoptotic signaling pathway. Pyroptosis form characterized formation membrane pores subsequent lysis well release pro-inflammatory contents mediated abscisin family. Studies have shown ferroptosis, necroptosis, pyroptosis are involved progression variety diseases, including tumors. In this review, we summarized advances occurrence, development, therapeutic OC.

Language: Английский

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