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Spatioselective Imaging of noncoding rnas in Mitochondria via an Organelle-Specific DNA Assembly Strategy

NANO LETTERS 2025年第5期25卷 1948-1955页

作者： Wu, Bo Zhao, Jian Yu, Fangzhi Li, Lele Zhao, Yuliang Natl Ctr Nanosci & Technol CAS Key Lab Biomed Effects Nanomat & Nanosafety Beijing 100190 Peoples R China Univ Chinese Acad Sci Coll Mat Sci & Optoelect Technol Beijing 100049 Peoples R China

Precise imaging of noncoding rnas (ncrnas) in specific organelles allows decoding of their functions at subcellular level but lacks advanced tools. Here we present a DNA-based nanobiotechnology for spatially selective imaging of ncRNA (e.g., microRNA (miRNA)) in mitochondria via an organelle-specific DNA assembly strategy. The target miRNA-initiated assembly of DNA hairpins is inhibited by the block of toehold-mediated strand displacement reaction but can be exclusively activated by a mitochondria-encoded ribosomal RNA (rRNA) for hybridization chain reaction, enabling spatial control over miRNA imaging. We demonstrate that the conditionally controlled DNA assembly technology allows for minimization of nonspecific activation and thus improves the spatial precision of miRNA detection. In addition, the strategy is adaptable to visualizing other ncrnas such as long noncoding rnas in mitochondria, highlighting the universality of the approach. Overall, this work provides a useful tool for spatially selective imaging of ncrnas and investigating the functions of organelle-located RNA.

关键词： noncoding rnas imaging mitochondria rrnas DNA assembly

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Regulation of Different Types of Cell Death by noncoding rnas: Molecular Insights and Therapeutic Implications

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ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE 2025年第5期8卷 1205-1226页

作者： Kumari, Reshmi Banerjee, Satarupa VIT Univ Sch Biosci & Technol Dept Biotechnol Vellore 632014 Tamil Nadu India

noncoding rnas (ncrnas) are crucial regulatory molecules in various biological processes, despite not coding for proteins. ncrnas are further divided into long noncoding rnas (lncrnas), micrornas (mirnas), and circular rnas (circrnas) based on the size of their nucleotides. These ncrnas play crucial roles in transcriptional, post-transcriptional, and epigenetic regulation. The regulatory roles of noncoding rnas, including lncrnas, mirnas, and circrnas, are essential in various modalities of cellular death, such as apoptosis, ferroptosis, cuproptosis, pyroptosis, disulfidptosis, and necroptosis. These noncoding rnas are integral to modulating gene expression and protein functionality during cellular death mechanisms. In apoptosis, lncrnas, mirnas, and circrnas influence the transcription of apoptotic genes. In ferroptosis, these noncoding rnas target genes and proteins involved in iron homeostasis and oxidative stress responses. For cuproptosis, noncoding rnas regulate pathways associated with the accumulation of copper ions, leading to cellular death. During pyroptosis, noncoding rnas modulate inflammatory mediators and caspases, affecting the proinflammatory cell death pathway. In necroptosis, noncoding rnas oversee the formation and functionality of necrosomes, thereby influencing the balance between cellular survival and death. Disulfidptosis is a unique type of regulated cell death caused by the excessive formation of disulfide bonds within cells, leading to cytoskeletal collapse and oxidative stress, especially under glucose-limited conditions. This investigation highlights the complex mechanisms through which noncoding rnas coordinate cellular death, emphasizing their therapeutic promise as potential targets, particularly in the domain of cancer treatment.

关键词： Cell death noncoding rnas Autophagy Breast cancer Post-transcriptional regulation

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noncoding rnas evolutionarily extend animal lifespan

GLOBAL MEDICAL GENETICS

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GLOBAL MEDICAL GENETICS 2025年第2期12卷 100034页

作者： Wang, Anyou Univ Memphis Feinstone Ctr Genom Res Memphis TN 38152 USA

The mechanisms underlying the evolution of lifespan across organisms remain mysterious. This study computes multiple large datasets and reveals that noncoding rnas (ncrnas), rather than proteins, drive animal lifespan evolution. Species in the animal kingdom evolutionarily increase their ncRNA length in their genomes, coinciding with trimming of the mitochondrial genome length. This leads to a low energy consumption and longevity. Notably, as species evolve and extend their lifespans, they tend to acquire long-lived ncRNA motifs while simultaneously losing short-lived ones, in contrast to the conservative patterns observed in protein evolution. These longevity-associated ncRNA motifs, such as GGTGCG, are particularly active in crucial tissues including the endometrium, ovaries, testes, and cerebral cortex. The ovary and endometrium carry more activating ncrnas than the testis, offering insight into why women generally outlive men. Taken together, ncrnas drive the evolution of the two most important traits of organisms: longevity and reproduction, and they execute many more fundamental functions than those conventionally thought. This discovery provides the foundation for combating longevity and aging.

关键词： noncoding rnas Evolution Extend Lifespan NcRNA Longevity Aging

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Revealing the Complex Interaction of noncoding rnas, Sirtuin Family, and Mitochondrial Function

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JOURNAL OF GENE MEDICINE 2025年第1期27卷 e70007页

作者： Yuan, Ludong Yin, Leijing Lin, Xiaofang Li, Jing Liang, Pengfei Jiang, Bimei Cent South Univ Xiangya Sch Med Dept Pathophysiol Sepsis Translat Med Key Lab Hunan Prov Changsha Hunan Peoples R China Cent South Univ Xiangya Hosp Dept Burns & Plast Surg Changsha Hunan Peoples R China Cent South Univ Natl Med Funct Expt Teaching Ctr Changsha Hunan Peoples R China

Mitochondria are key organelles that perform and coordinate various metabolic processes in the cell, and their homeostasis is essential for the maintenance of eukaryotic life. To maintain mitochondrial homeostasis and cellular health, close communication between noncoding rnas (ncrnas) and proteins is required. For example, there are numerous crosstalk between ncrnas and the sirtuin (SIRT1-7) family, which is a group of nicotinamide adenine dinucleotides (NAD(+))-dependent Type III deacetylases. Ncrnas are involved in the regulation of gene expression of sirtuin family members, and deacetylation of sirtuin family members can also influence the generation of ncrnas. This review focuses on the relationship between the two mentioned above and summarizes the impact of their interactions on mitochondrial metabolism, oxidative stress, mitochondrial apoptotic pathways, mitochondrial biogenesis, mitochondrial dynamics, and other mitochondria-related pathophysiological processes. Finally, the review also describes targeted and appropriate treatment strategies. In conclusion, we provide an overview of the ncRNA-sirtuins/mitochondria relationship that could provide a reference for related research in the mitochondrial field and help the future development of new biomedical applications in this area.

关键词： apoptosis metabolism mitochondria noncoding rnas oxidative stress sirtuins

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noncoding rnas as therapeutic targets in atherosclerosis with diabetes mellitus

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CARDIOVASCULAR THERAPEUTICS 2018年第4期36卷 e12436-e12436页

作者： Tang, Ningning Jiang, Shaoyan Yang, Yanyan Liu, Shaoyan Ponnusamy, Murugavel Xin, Hui Yu, Tao Qingdao Univ Inst Translat Med Qingdao Peoples R China Qingdao Univ Affiliated Cardiovasc Hosp Dept Cardiol Qingdao Peoples R China Qingdao Univ Affiliated Hosp Dept Cardiol Qingdao Peoples R China

Atherosclerosis is one of the major macrovascular complications of diabetes mellitus (DM), and it is the main cause of death from clinical observation. Among various cell types involved in this disorder, endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages play a crucial role in the occurrence and development of this disease. The regulation and stabilization of these cells are a key therapeutic strategy for DM-associated atherosclerosis. An increasing number of evidences implicate that various types of noncoding rnas (ncrnas) play a vital role in many cellular responses as well as in physiological and pathological processes of atherosclerosis and DM that drive atherogenic/antiatherogenic processes in those cells. Encouragingly, many ncrnas have already been tested in animal experiments or clinical trials showing good performance. In this review, we summarize recent progresses in research on functional regulatory role of ncrnas in atherosclerosis with DM. More importantly, we illustrate new thoughts and findings relevant to ncrnas as potential therapeutic targets or biomarkers for atherosclerosis with DM.

关键词： biomarkers cardiovascular diabetes mellitus noncoding rnas targets

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noncoding rnas in acute kidney injury

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KIDNEY INTERNATIONAL 2018年第5期94卷 870-881页

作者： Brandenburger, Timo Somoza, Antonio Salgado Devaux, Yvan Lorenzen, Johan M. Univ Hosp Duesseldorf Dept Anesthesiol Moorenstr 5 D-40225 Dusseldorf Germany Luxembourg Inst Hlth Cardiovasc Res Unit Dept Populat Hlth Luxembourg Luxembourg Univ Zurich Hosp Div Nephrol Zurich Switzerland

Acute kidney injury (AKI) is an important health issue concerning similar to 50% of patients treated in intensive care units. AKI mainly occurs after sepsis, acute ischemia, nephrotoxicity, or hypoxia and leads to severe damage of the kidney and to an increased risk of mortality. The diagnosis of AKI is currently based on creatinine urea levels and diuresis. Yet, novel markers may improve the accuracy of this diagnosis at an early stage of the disease, thereby allowing early prevention and therapy, ultimately leading to a reduction in the need for renal replacement therapy and decreased mortality. Non-protein-coding rnas or noncoding rnas are central players in development and disease. They are important regulatory molecules that allow a fine-tuning of gene expression and protein synthesis. This regulation is necessary to maintain homeostasis, and its dysregulation is often associated with disease development. noncoding rnas are present in the kidney and in body fluids and their expression is modulated during AKI. This review article assembles the current knowledge of the role of noncoding rnas, including micrornas, long noncoding rnas and circular rnas, in the pathogenesis of AKI. Their potential as biomarkers and therapeutic targets as well as the challenges to translate research findings to clinical application are discussed. Although micrornas have entered clinical testing, preclinical and clinical trials are needed before long noncoding rnas and circular rnas may be considered as useful biomarkers or therapeutic targets of AKI.

关键词： acute kidney injury biomarkers circular rnas diagnosis long noncoding rnas micrornas noncoding rnas prevention therapeutics

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noncoding rnas in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets

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中国药理学报（英文版） 2021年第4期42卷 499-507页

作者： Hong-ge Fa Wen-guang Chang Xue-juan Zhang Dan-dan Xiao Jian-xun Wang School of Basic Medical Sciences Qingdao UniversityQingdao 266021China Institute for Translational Medicine Qingdao UniversityQingdao 266021China Institute for Translational Medicine Qingdao UniversityQingdao 266021China Department of General Practice Affiliated HospitalQingdao UniversityQingdao 266021China School of Basic Medical Sciences Qingdao UniversityQingdao 266021China

Anthracyclines,such as doxorubicin(DOX),are well known for their high efficacy in treating multiple cancers,but their clinical usage is limited due to their potential to induce fatal *** detrimental effects significantly impact the overall physical condition or even induce the morbidity and mortality of cancer ***,it is extremely important to understand the mechanisms of DOX-induced cardiotoxicity to develop methods for the early detection of cytotoxicity and therapeutic *** have shown that many molecular events are involved in DOX-induced ***,the precise mechanisms are still not completely ***,noncoding rnas(ncrnas)have been extensively studied in a diverse range of regulatory roles in cellular physiological and pathological *** respect to their roles in DOX-induced cardiotoxicity,micrornas(mirnas)are the most widely studied,and studies have focused on the regulatory roles of long noncoding rnas(Incrnas)and circular rnas(circrnas),which have been shown to have significant functions in the cardiovascular *** discoveries on the roles of ncrnas in DOX-induced cardiotoxicity have prompted extensive interest in exploring candidate ncrnas for utilization as potential therapeutic targets and/or diagnostic *** review presents the frontier studies on the roles of ncrnas in DOX-induced cardiotoxicity,addresses the possibility and prospects of using ncrnas as diagnostic biomarkers or therapeutic targets,and discusses the possible reasons for related discrepancies and limitations of their use.

关键词： noncoding rnas doxorubicin cardiotoxicity biomarkers

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noncoding rnas and programmed cell death in hepatocellular carcinoma: Significant role of epigenetic modifications in prognosis, chemoresistance, and tumor recurrence rate

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CELL BIOLOGY INTERNATIONAL 2024年第5期48卷 556-576页

作者： Arefnezhad, Reza Ashna, Sara Rezaei-Tazangi, Fatemeh Arfazadeh, Seyed Mahdi Seyedsalehie, Seyede Shabnam Yeganeafrouz, Shaghayegh Aghaei, Melika Sanandaji, Mandana Davoodi, Ramin Abadi, Sareh Ranjbar Karim Vosough, Massoud Coenzyme R Res Inst Tehran Iran Shiraz Univ Med Sci Student Res Comm Shiraz Iran Islamic Azad Univ Student Res Comm Sci & Res Branch Tehran Iran Fasa Univ Med Sci Sch Med Dept Anat Fasa Iran Ahvaz Jundishapur Univ Med Sci Fac Med Dept Pediat Ahvaz Iran Islamic Azad Univ Fac Med Dept Med Sci Med Branch Tehran Iran Islamic Azad Univ Dept Biol Sci & Res Branch Tehran Iran Univ Tehran Dept Phys Educ & Sport Sci Tehran Iran Univ Tehran Microbiol Dept Tehran Iran ACECR Royan Inst Stem Cell Biol & Technol Cell Sci Res Ctr Dept Regenerat Med Tehran Iran Karolinska Inst Inst Lab Med Expt Canc Med Huddinge Sweden

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high death rate in the world. The molecular mechanisms related to the pathogenesis of HCC have not been precisely defined so far. Hence, this review aimed to address the potential cross-talk between noncoding rnas (ncrnas) and programmed cell death in HCC. All related papers in the English language up to June 2023 were collected and screened. The searched keywords in scientific databases, including Scopus, PubMed, and Google Scholar, were HCC, ncrnas, Epigenetic, Programmed cell death, Autophagy, Apoptosis, Ferroptosis, Chemoresistance, Tumor recurrence, Prognosis, and Prediction. According to the reports, ncrnas, comprising long ncrnas, micrornas, circular rnas, and small nucleolar rnas can affect cell proliferation, migration, invasion, and metastasis, as well as cell death-related processes, such as autophagy, ferroptosis, necroptosis, and apoptosis in HCC by regulating cancer-associated genes and signaling pathways, for example, phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase/MAPK, and Wnt/beta-catenin signaling pathways. It seems that ncrnas, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients. However, more scientific evidence is suggested to be accomplished to confirm these results. noncoding RNA (Ncrnas) can affect cell proliferation, migration, invasion, and metastasis, as well as cell death-related processes in hepatocellular carcinoma (HCC). Autophagy, ferroptosis, necroptosis, and apoptosis are influenced by ncrnas in HCC by regulating associated signaling pathways. Ncrnas, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients.

关键词： chemoresistance hepatocellular carcinoma noncoding rnas programmed cell death therapeutic strategies tumor recurrence

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noncoding rnas in protein clearance pathways: implications in neurodegenerative diseases

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JOURNAL OF GENETICS 2017年第1期96卷 203-210页

作者： Sengupta, Sonali VIT Univ Sch Biosci & Technol Div Biomol & Genet Vellore 632014 Tamil Nadu India

The importance of noncoding genome has become more evident in recent years. Before genome sequencing, the most well studied portion of our genome was protein coding genes. Interestingly, this coding portion accounted only for 1.5% of the genome, the rest being the noncoding sequences. noncoding rnas (ncrnas) are involved in normal cell physiology, stress, and disease states. A class of small ncrnas and mirnas has gained much importance because of its involvement in human diseases such as cancer. Involvement of long ncrnas have also been acknowledged in other human diseases, especially in neurodegenerative diseases. Neurodegenerative diseases are characterized by the presence of abnormally folded proteins that are toxic to the cell. Several studies from model organisms suggest upregulation of pathways that clear this toxic protein may provide protection against neurodegeneration. In this review, I summarize the importance of ncrnas in protein quality control system of cell that is implicated in this fatal group of neurodegenerative diseases.

关键词： noncoding rnas autophagy ubiquitin proteasomal system microRNA polyQ

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noncoding rnas in breast cancer

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BRIEFINGS IN FUNCTIONAL GENOMICS 2016年第3期15卷 200-221页

作者： Lo, Pang-Kuo Wolfson, Benjamin Zhou, Xipeng Duru, Nadire Gernapudi, Ramkishore Zhou, Qun Univ Maryland Baltimore Dept Biochem & Mol Biol Baltimore MD USA Univ Maryland Baltimore Program Mol Med Noncoding RNAs Adipogenesis Breast Canc Baltimore MD USA Univ Maryland Baltimore Dept Biochem & Mol Biol Noncoding RNAs Adipogenesis Breast Canc Baltimore MD USA Jiangsu Univ Med Clin Sch Med Zhenjiang 202013 Jiangsu Peoples R China Univ Maryland Baltimore Epigenet Regulat & Canc Stem Cells Breast Canc Baltimore MD USA Univ Maryland Baltimore Noncoding RNAs Adipogenesis Breast Canc Baltimore MD USA Univ Maryland Baltimore Biochem & Mol Biol Baltimore MD USA

The mammalian transcriptome has recently been revealed to encompass a large number of noncoding rnas (ncrnas) that play a variety of important regulatory roles in gene expression and other biological processes. Micrornas (mirnas), the best studied of the short noncoding rnas (sncrnas), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncrnas called piwi-interacting rnas (pirnas) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding rnas (lncrnas) of > 200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncrnas (including mirnas and pirnas) and lncrnas in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncrnas. Moreover, the current and potential future applications of ncrnas to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics.

关键词： noncoding rnas micrornas piwi-interacting rnas long noncoding rnas breast cancer

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