Pathological expression of mitochondrial genome-derived circRNA SCAR/mc-COX2 and its ceRNA network in colorectal cancer: implications for clinical significance

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Март 14, 2025

Mitochondrial-encoded circular RNAs (mecciRNAs) are a newly discovered class of mitochondrial-encoded non-coding (mt-ncRNAs) that play important biological roles in the cell. This study aimed to examine expression profile SCAR/mc-COX2 (has_circ_0089762) colorectal cancer (CRC) and its relationship with clinicopathological variables. Furthermore, better understand SCAR/mc-COX2's functional role CRC, we constructed competing endogenous RNA (ceRNA) network. Quantitative real-time PCR (qRT-PCR) was employed analyze levels 40 pairs CRC samples, consisting tumor samples adjacent non-tumoral from patients. The ceRNA regulatory network using online bioinformatics tools. Kyoto Encyclopedia Genes Genomes (KEGG) pathway analysis Gene Ontology (GO) enrichment were conducted Enrichr database. results demonstrated significant decrease tissues compared (p-value<0.05). In another finding, observed between pathological T staging status (p-value=0.02). Additionally, Receiver Operating Characteristic (ROC) curve revealed had an area under (AUC) 0.77, 80% sensitivity 75% specificity. Finally, including SCAR/mc-COX2, 5 miRNA, 9 mRNAs found. These findings suggest may act as suppressor dysregulation could crucial pathophysiology this cancer. association robust diagnostic performance (AUC = 80%, specificity 75%) highlight potential novel biomarker for detection prognosis. Further studies required elucidate precise tumorigenesis clinical applicability.

Язык: Английский

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Emerging roles of epigenetics in lead-induced neurotoxicity

Environment International, Год журнала: 2023, Номер 181, С. 108253 - 108253

Опубликована: Окт. 13, 2023

Lead is a common environmental heavy metal contaminant. Humans are highly susceptible to lead accumulation in the body, which causes nervous system damage and leads variety of diseases, such as Alzheimer's disease, Parkinson's autism spectrum disorder. Recent research has focused on mechanisms lead-induced neurotoxicity at multiple levels, including DNA methylation, histone modifications, non-coding RNAs, involved various diseases. We reviewed latest articles summarised emerging roles modification, RNAs neurotoxicity. Our summary provides theoretical basis directions for future prevention, diagnosis, treatment neurological

Язык: Английский

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Unraveling the nexus of age, epilepsy, and mitochondria: exploring the dynamics of cellular energy and excitability

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 5, 2024

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible energy production and calcium regulation. This review offers an in-depth examination of interplay between epilepsy, mitochondrial function, aging. Many factors might account correlation epilepsy Mitochondria, integral to dynamics neuronal excitability, perform critical role in pathophysiology epilepsy. The mechanisms linking mitochondria are multifaceted, involving dysfunction, reactive oxygen species (ROS), dynamics. Mitochondrial dysfunction can trigger seizures compromising ATP production, increasing glutamate release, altering ion channel function. ROS, natural byproducts respiration, contribute oxidative stress neuroinflammation, epileptogenesis. govern fusion fission processes, influence seizure threshold buffering, impact propagation. Energy demands during highlight generation maintaining membrane potential. handling dynamically modulates affecting synaptic transmission action potential generation. Dysregulated hallmark contributing excitotoxicity. Epigenetic modifications function through histone modifications, DNA methylation, non-coding RNA expression. Potential therapeutic avenues targeting include mitochondria-targeted antioxidants, ketogenic diets, metabolic therapies. concludes outlining future directions research, emphasizing integrative approaches, advancements ethical considerations. Mitochondria emerge as central players narrative offering profound insights this challenging disorder.

Язык: Английский

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RNA G-quadruplex in functional regulation of noncoding RNA: Challenges and emerging opportunities

Cell chemical biology, Год журнала: 2023, Номер 31(1), С. 53 - 70

Опубликована: Окт. 30, 2023

Язык: Английский

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tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators

Biomolecules, Год журнала: 2024, Номер 14(10), С. 1340 - 1340

Опубликована: Окт. 21, 2024

As the most ancient RNA, transfer RNAs (tRNAs) play a more complex role than their constitutive function as amino acid transporters in protein synthesis process. The transcription and maturation of tRNA cells are subject to stringent regulation, resulting formation tissue- cell-specific pools with variations overall abundance, composition, modification, charging levels. heterogeneity contributes facilitating histocyte-specific expression patterns is involved diverse biological processes. Moreover, tRNAs can be recognized by various RNase under physiological pathological conditions generate tRNA-derived small (tsRNAs) serve regulatory Here, we summarize these recent insights into highlight advances regulation tsRNA biogenesis modifications. We synthesize mechanisms embryonic development, cell fate determination, epigenetic inheritance regulation. also discuss potential clinical applications based on new knowledge diagnostic prognostic biomarkers therapeutic strategies for multiple diseases.

Язык: Английский

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Plumbing mysterious RNAs in “dark genome” for the conquest of human diseases

Molecular Therapy, Год журнала: 2023, Номер 31(6), С. 1577 - 1595

Опубликована: Май 10, 2023

Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion noncoding RNAs (ncRNAs). Among these, long (lncRNAs) represent the largest group and pervasively throughout genome. Dysfunctions in lncRNAs have been found various diseases, highlighting their potential as therapeutic, diagnostic, prognostic targets. However, challenges, such unknown molecular mechanisms nonspecific immune responses, issues drug specificity delivery present obstacles translating clinical applications. In this review, we summarize recent publications explored lncRNA functions human diseases. We also discuss challenges future directions for developing treatments, aiming to bridge gap between functional studies inspire further exploration field.

Язык: Английский

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Hypoxia-induced circRNAs encoded by PPARA are highly expressed in human cardiomyocytes and are potential clinical biomarkers of acute myocardial infarction

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Март 12, 2024

Abstract Background Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but biological mechanism their involvement clinical significance remain unknown. We aimed to identify circRNAs significantly associated with morbidity peripheral blood patients AMI evaluate diagnostic utility. Methods High-throughput sequencing was used screen for differentially expressed samples obtained from five sex- age-matched healthy controls. A series bioinformatics tools databases were determine functional classification pathway enrichment based on data sequencing. hypoxia model established effect circRNA expression cardiomyocytes. cytoplasmic separation assay enzyme resistance employed characteristics circRNA. Polymerase chain reaction validity testing receiver operating characteristic (ROC) curve analysis utility assessments diagnosis AMI. Results large number found be more these highly than lowly expressed. The genes encoding have wide range effects various functions body. hypoxic environment promoted upregulation cardiomyocytes, hsa_circ_0116795 encoded by PPARA In terms characteristics, under conditions, (circ_PPARA) mainly located cytoplasm cardiomyocytes resistant exonuclease. ROC showed levels circ_PPARA different those Conclusion abnormally detectable particular, cells its indicate it could as biomarker early

Язык: Английский

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Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review)

Molecular Medicine Reports, Год журнала: 2025, Номер 31(3)

Опубликована: Янв. 24, 2025

Renowned as a highly invasive and lethal tumor derived from neural stem cells in the central nervous system, glioblastoma (GBM) exhibits substantial histopathological variation genomic complexity, which drive its rapid progression therapeutic resistance. Alterations mitochondrial DNA (mtDNA) copy number (CN) serve crucial role GBM development progression, affecting various aspects of biology, including energy production, oxidative stress regulation cellular adaptability. Fluctuations mtDNA levels, whether elevated or diminished, can impair function, potentially disrupting phosphorylation amplifying reactive oxygen species generation, thereby fueling growth influencing treatment responses. Understanding mechanisms mtDNA‑CN variations, their interplay with genetic environmental elements microenvironment, is essential for advancing diagnostic strategies. Targeting alterations could strengthen efficacy, mitigate resistance ultimately enhance prognosis patients this aggressive brain tumor. The present review summarizes existing literature on alterations, specifically emphasizing variations association by surveying articles published between 1996 2024, sourced databases such Scopus, PubMed Google Scholar. In addition, provides brief overview genome architecture, knowledge regarding integrity CN, how mitochondria significantly impact tumorigenesis. This further presents information approaches restoring that contribute to optimized function improved health outcomes.

Язык: Английский

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Targeting Regulatory Noncoding RNAs in Human Cancer: The State of the Art in Clinical Trials

Pharmaceutics, Год журнала: 2025, Номер 17(4), С. 471 - 471

Опубликована: Апрель 4, 2025

Noncoding RNAs (ncRNAs) are a heterogeneous group of RNA molecules whose classification is mainly based on arbitrary criteria such as the molecule length, secondary structures, and cellular functions. A large fraction these ncRNAs play regulatory role regarding messenger (mRNAs) or other ncRNAs, creating an intracellular network cross-interactions that allow fine complex regulation gene expression. Altering balance between interactions may be sufficient to cause transition from health disease vice versa. This leads possibility intervening in mechanisms re-establish patients. The associated with all cancer hallmarks, proliferation, apoptosis, invasion, metastasis, genomic instability. Based function performed carcinogenesis, behave either oncogenes tumor suppressors. However, this distinction not rigid; some can fall into both classes depending tissue considered target molecule. Furthermore, them also involved regulating response traditional cancer-therapeutic approaches. In general, molecular by very still largely unclear, but it has enormous potential for development new therapies, especially cases where methods fail, their use novel more efficient biomarkers. Overall, review will provide brief overview human biology, specific focus describing most recent ongoing clinical trials (CT) which have been tested therapeutic agents evaluated

Язык: Английский

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Mitochondrial microRNAs (mitomiRs) as emerging biomarkers and therapeutic targets for chronic human diseases

Frontiers in Genetics, Год журнала: 2025, Номер 16

Опубликована: Апрель 25, 2025

Mitochondria are membrane-bound cell organelles that undertake the majority of energetic and metabolic processes within cell. They also responsible for mediating multiple apoptotic pathways, balancing redox charges, scavenging reactive oxygen species. MicroRNAs, which short, non-coding RNAs widely known regulating gene expression at post-transcriptional level, regulate many these processes. The specific microRNAs directly or indirectly control mitochondrial dynamics called miRNAs (mitomiRs). broadest classification this type ncRNA encompasses nuclear-encoded interact with cytoplasmatic mRNAs associated activity. At same time, a more subset comprises translocate into mitochondria to inside organelle. Finally, smallest group mitomiRs includes those codified by mtDNA can endogenous transcripts be transported cytoplasm modulate circulating mRNAs. Regardless origin action mechanism, have been recently recognized key role in progression variety chronic disorders, such as neurodegenerative cardiovascular diseases, diabetes, asthma, depression, even cancer. All progressive pathologies tightly linked dysregulation. further an aberrant cellular metabolism, positioning reliable biomarkers diagnosing several diseases. These molecular indicators provided insights how conditions progress, allowing development different miRNA-based treatment strategies target dysregulated mitochondrial-related genes, reestablishing their baseline activity restricting disease progression.

Язык: Английский

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