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Circadian genes and non-coding rnas: interactions and implications in cancer

ANIMAL CELLS AND SYSTEMS 2025年第1期29卷 135-148页

作者： Yoon, Goeun Roh, Jungwook Jang, Wonyi Kim, Wanyeon Korea Natl Univ Educ Dept Sci Educ Cheongju South Korea Seowon Univ Dept Biol Educ Cheongju South Korea Korea Natl Univ Educ Dept Biol Educ 250 Taeseongtabyeon ro Cheongju 28173 Chungbuk South Korea

Circadian rhythms are 24-hour cycles in various biological processes, such as sleep, wake, and hormone secretion, controlled by an internal clock. Disruption of circadian rhythms has been related to various human diseases. Abnormal expression of circadian rhythm-related genes, such as CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, ROR alpha, NPAS2, REV-ERB alpha and TIMELESS has also been reported to be associated with cancer. CLOCK, CRY1, NPAS2 and TIMELESS are related to cancer development. In contrast, BMAL1, PER1, PER2, CRY2, ROR alpha and REV-ERB alpha related to inhibit cancer development and progression. Furthermore, studies suggest that circadian genes related to cancer can be regulated by ncrnas such as mirnas, lncrnas and circrnas and that dysregulation of these ncrnas contributes to cancer development. Here, we summarize the mechanisms whereby ncrna dysregulation leads to the abnormal expression of circadian genes in several cancers and the ncrna and circadian gene-associated regulatory mechanisms that contribute to resistance to chemo - and radiotherapy. This review provides insights into the mechanistic involvements of the regulatory network of circadian genes and ncrnas in cancer development.

关键词： Circadian gene non-coding rna cancer circadian rhythm

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Liquid biopsy using non-coding rnas and extracellular vesicles for breast cancer management

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BREAST CANCER 2025年第1期32卷 16-25页

作者： Hashimoto, Kazuki Ochiya, Takahiro Shimomura, Akihiko Natl Ctr Global Hlth & Med Dept Breast Surg Oncol 1-21-1 Toyama Shinjuku Ku Tokyo 1628655 Japan Tokyo Med Univ Inst Med Sci Dept Mol & Cellular Med 6-7-1 Nishishinjuku Shinjuku Ku Tokyo 1600023 Japan Natl Ctr Global Hlth & Med Dept Breast & Med Oncol 1-21-1 Toyama Shinjuku Ku Tokyo 1628655 Japan

This article examines liquid biopsy using non-coding rnas and extracellular vesicles in detail. Liquid biopsy is emerging as a prominent non-invasive diagnostic tool in the treatment of breast cancer. We will elucidate the roles of these molecules in early detection, monitoring treatment effectiveness, and prognostic assessment of breast cancer. Additionally, the clinical significance of these molecules will be discussed. We aim to delve into the distinct characteristics of these molecules and their possible roles in breast cancer management, with an anticipation of their contribution to future diagnostic and therapeutic advancements.

关键词： Breast cancer Liquid biopsy mirna non-coding rna Extracellular vesicles

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Exploration of non-coding rnas related to intramuscular fat deposition in Xinjiang Brown cattle and Angus x Wagyu cattle

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BMC GENOMICS 2025年第1期26卷 1-20页

作者： Zhou, Yuxin Ren, Wanping Shao, Wei Gao, Yu Yao, Kangyu Yang, Min Zhang, Xinyu Wang, Yiran Li, Fengming Yang, Liang Xinjiang Agr Univ Coll Anim Sci Xinjiang Key Lab Meat & Milk Prod Herbivore Nutr Urumqi 830052 Peoples R China

non-coding rnas (ncrnas) serve as crucial regulatory elements in the process of adipogenesis in animals;however, the specific roles and interrelationships of ncrnas in bovine fat deposition remain poorly understood. This study aims to investigate the differentially expressed ncrnas in the longissimus dorsi muscle of Xinjiang Brown cattle (XB) and Angus x\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\times$$\end{document} Wagyu cattle (AW), to elucidate the regulatory mechanisms underlying lipidogenesis that may involve ncrnas. Four Xinjiang Brown cattle and four Angus x\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\times$$\end{document} Wagyu cattle were selected, ensuring they are subjected to identical feeding conditions, in order to evaluate the intermuscular fat (IMF) of longissimus dorsi muscles. The fat content of muscle tissue was quantified using the Soxhlet extraction method, revealing that the fat levels in the AW group were significantly elevated compared to those in the XB group. Taking muscle samples for paraffin sectioning and observing their morphology, it was found that the fat richness of the AW group was significantly higher than that of the XB group. Utilizing high-throughput rna sequencing technology, we conducted an extensive transcriptomic analysis of longissimus dorsi muscles of XB and AW to identify significant ncrnas implicated in fat metabolism and adipogenesis. The mirna analysis yielded between 109,343,831 117,258,570 clean reads, whereas the lncrna and circrna analyses produced between 81,607,756 102,917,174 clean reads. Subsequent analysis revealed the identification of 53 di

关键词： Xinjiang brown cattle Wagyu Intermuscular fat Adipogenesis non-coding rna

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Role of non-coding rnas in Rheumatoid Arthritis and Supervision Mechanism of Chinese Medicine

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CHINESE JOUrnaL OF INTEGRATIVE MEDICINE 2025年 1-11页

作者： Li, Shu Fang, Hao-xiang Wan, Lei Liu, Jian Anhui Univ Chinese Med Affiliated Hosp 1 Dept Rheumal Hefei 230031 Peoples R China Anhui Univ Chinese Med Clin Med Coll 1 Hefei 230038 Peoples R China Xinan Inst Med & Modernizat Tradit Chinese Med Hefei 230012 Peoples R China Xinan Med Educ Dept Key Lab Hefei 230012 Peoples R China

The prevalence of rheumatoid arthritis (RA) has sharply increased in recent years, posing a serious threat to human health. RA is characterized as a chronic, multisystem disease with morning stiffness and symmetric small joint pain. However, its fundamental processes are poorly understood. With the advancements in molecular biology techniques, a growing body of research indicates that numerous non-coding rnas (ncrnas) are essential for the pathogenesis of RA. These ncrnas not only contribute to the onset of RA but also play a role in the pathological processes of RA development, including synovial immune inflammation and bone destruction. Chinese medicine (single compounds, single herbs, and compound formulae, as well as non-drug therapies such as acupuncture and moxibustion), offer significant benefits for treating RA. This study examined the role of 3 different ncrna types (circular rna, long ncrna, and microrna) as biomarkers in RA diagnosis, as well as their regulatory roles in rheumatoid arthritis fibroblast-like synoviocytes functions such as inflammatory response, proliferation, cell cycle, apoptosis, and invasion. Additionally, the study explored the mechanisms by which Chinese medicine regulates these ncrnas, with the goal of offering innovative strategies for RA treatment.

关键词： rheumatoid arthritis non-coding rna mechanisms of action Chinese medicine review

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rna sequencing of transcriptomes in human brain regions: protein-coding and non-coding rnas, isoforms and alleles

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BMC GENOMICS 2015年第1期16卷 1-16页

作者： Webb, Amy Papp, Audrey C. Curtis, Amanda Newman, Leslie C. Pietrzak, Maciej Seweryn, Michal Handelman, Samuel K. Rempala, Grzegorz A. Wang, Daqing Graziosa, Erica Tyndale, Rachel F. Lerman, Caryn Kelsoe, John R. Mash, Deborah C. Sadee, Wolfgang Ohio State Univ Coll Med Ctr Pharmacogen Columbus OH 43210 USA Ohio State Univ Dept Biomed Informat Coll Med Columbus OH 43210 USA Ohio State Univ Coll Publ Hlth Div Biostat Columbus OH 43210 USA Ohio State Univ Math Biosci Inst Columbus OH 43210 USA Thermo Fisher Sci San Francisco CA 94080 USA Univ Toronto Ctr Addict & Mental Hlth Toronto ON Canada Univ Toronto Dept Psychiat Toronto ON Canada Univ Toronto Dept Pharmacol & Toxicol Toronto ON Canada Univ Penn Dept Psychiat Annenberg Sch Commun Philadelphia PA 19104 USA Univ Penn Abramson Canc Ctr Philadelphia PA 19104 USA Univ Calif San Diego Lab Psychiat Genom Dept Psychiat San Diego CA 92103 USA VA San Diego Healthcare Syst San Diego CA USA Univ Miami Miller Sch Med Dept Neurol Miami FL 33136 USA Ohio State Univ Coll Med Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Pharm Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Dept Pharmacol Columbus OH 43210 USA Ohio State Univ Coll Med Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Pharm Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Sci Dept Psychiat Columbus OH 43210 USA Ohio State Univ Coll Med Dept Human Genet Columbus OH 43210 USA Ohio State Univ Coll Med Dept Internal Med Columbus OH 43210 USA Ohio State Univ Coll Pharm Columbus OH 43210 USA Ohio State Univ Coll Environm Hlth Sci Columbus OH 43210 USA

Background: We used rna sequencing to analyze transcript profiles of ten autopsy brain regions from ten subjects. rna sequencing techniques were designed to detect both coding and non-coding rna, splice isoform composition, and allelic expression. Brain regions were selected from five subjects with a documented history of smoking and five non-smokers. Paired-end rna sequencing was performed on SOLiD instruments to a depth of >40 million reads, using linearly amplified, ribosomally depleted rna. Sequencing libraries were prepared with both poly-dT and random hexamer primers to detect all rna classes, including long non-coding (lncrna), intronic and intergenic transcripts, and transcripts lacking poly-A tails, providing additional data not previously available. The study was designed to generate a database of the complete transcriptomes in brain region for gene network analyses and discovery of regulatory variants. Results: Of 20,318 protein coding and 18,080 lncrna genes annotated from GENCODE and lncipedia, 12 thousand protein coding and 2 thousand lncrna transcripts were detectable at a conservative threshold. Of the aligned reads, 52 % were exonic, 34 % intronic and 14 % intergenic. A majority of protein coding genes (65 %) was expressed in all regions, whereas ncrnas displayed a more restricted distribution. Profiles of rna isoforms varied across brain regions and subjects at multiple gene loci, with neurexin 3 (NRXN3) a prominent example. Allelic rna ratios deviating from unity were identified in >400 genes, detectable in both protein-coding and non-coding genes, indicating the presence of cis-acting regulatory variants. Mathematical modeling was used to identify rnas stably expressed in all brain regions (serving as potential markers for normalizing expression levels), linked to basic cellular functions. An initial analysis of differential expression analysis between smokers and nonsmokers implicated a number of genes, several previously associated with nicotin

关键词： rna sequencing Brain regions Differential expression Allelic expression imbalance Isoform fraction non-coding rna

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rna binding proteins mediate axonal delivery of non-coding rnas and regulate axon growth

RNA binding proteins mediate axonal delivery of non-coding R...

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中国神经科学学会第十二届全国学术会议

作者： Lan Bao Bin Wang State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell Science Institute of Biochemistry and Cell Biology Chinese Academy of Sciences

rna binding proteins(RBPs) have been implicated as cytoskeletal adaptors that act via a form of ribonucleoprotein(RNP) granules that carry mrnas into the dendrite or axon. FMRP is an rna-binding protein that is encoded by Fmr1, the absence of which causes dysregulated neuronal disorders, including mental retardation and autism spectrum disorders. FMRP is also reported to be associated with mrnas in the rnainduced silencing complex(RISC) and to thereby potentially be involved in the mirnamediated regulation of activity-dependent protein synthesis. We reveal a mechanism that FMRP-mediated axonal delivery of miR-181 d regulates axon elongation by locally targeting Map1 b and Calm1 in primary sensory neurons. FMRP was associated with miR-181 d and its targets MAP1 B mrna(Map1 b) and calmodulin mrna(Calm1). The downregulation of FMRP in Fmr1 mice or in the cell bodies of cultured dorsal root ganglion(DRG) neurons impaired the axonal delivery of miR-181 d with Map1 b and Calm1, leading to decreased protein levels of MAP1 B and calmodulin in axons. At the same time, nerve growth factor(NGF) increased the local synthesis of MAP1 B and calmodulin in axons by releasing Map1 b and Calm1 from FMRP and miR-181 drepressing granules. Furthermore, several RBPs were detected to localize in the axon of primary sensory neuron and involved in axonal delivery of different mirnas. The functions of these RBPs and delivered mirnas need to be further investigated.

关键词： rna binding protein FMRP miR-181d non-coding rna axonal delivery primary sensory neuron

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Integrative analysis of glioblastoma multiforme: the power of non-coding rnas and hub genes in cancer research

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Clinical and Experimental Medicine 2025年第1期25卷 1-14页

作者： Golestanifar, Ahmad Lajmiri, Hossein Saberiyan, Mohammadreza Department of Medical Genetics Faculty of Medicine School of Medical Sciences Hormozgan University of Medical Sciences P.O. Box *** Bandar Abbas Iran Department of Medical Microbiology (Bacteriology and Virology) Afzalipour Faculty of Medicine Kerman University of Medical Sciences Kerman Iran

This study aims to dissect the complex molecular landscape of glioblastoma multiforme (GBM), focusing on identifying key regulatory non-coding rnas and protein-coding genes that could serve as therapeutic targets and prognostic biomarkers. GBM is an aggressive form of brain cancer characterized by poor prognosis and limited treatment options. Recent advances in high-throughput genomic technologies have opened new avenues for understanding the molecular underpinnings of GBM, with a particular focus on the roles of ncrnas. We utilized multiple datasets from the NCBI Gene Expression Omnibus (GEO) to analyze mrna, mirna, lncrna, and circrna expression profiles in GBM versus normal brain tissues. Differential expression analysis was conducted using GEO2R, followed by pathway enrichment and protein–protein interaction (PPI) network analyses using DAVID and STRING databases, respectively. Hub genes were identified and validated through GEPIA2, and a competing endogenous rna (cerna) network was constructed to elucidate the interactions between non-coding rnas (ncrnas) and protein-coding genes. The study identified several differentially expressed genes and ncrnas, highlighting complex interactions within the PPI network and significant pathway enrichments implicated in GBM progression. The cerna network analysis revealed potential regulatory axes mediated by ncrnas. Validation of hub genes confirmed their differential expression and prognostic value. Additionally, correlations between gene expression, drug sensitivity, and immune cell infiltration were analyzed, offering insights into personalized therapeutic approaches. Our findings underscore the intricate molecular networks in GBM, emphasizing the role of ncrnas in tumor biology and their potential as therapeutic targets. The study highlights the necessity for further experimental validation of bioinformatics predictions to bridge the gap between genomic insights and clinical application, ultimately aiming to enhance the

关键词： Bioinformatics analysis circrna/lncrna-mirna-mrna Glioblastoma multiforme non-coding rna rna-seq

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Effect of novel non-coding small rna111 of Pseudomonas aeruginosa on bacterial virulence

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MICROBIAL PATHOGENESIS 2024年 197卷 107077页

作者： Wang, Fanghong Li, Qiwei Li, Song Zhou, Peng Ma, Peng Wang, Lan Liu, Yaqin Guo, Zhongzhong Liu, Hongwei Li, Youqiang Yin, Weiguo Han, Juanjuan Dali Univ Coll Basic Med Dali 671000 Peoples R China Guangzhou Med Univ Affiliated Qingyuan Hosp Qingyuan Peoples Hosp Dept Lab Med Qingyuan 511518 Peoples R China Guangzhou Univ Chinese Med Affiliated Hosp 2 Dept Lab Med Guangzhou 510120 Peoples R China Southern Med Univ Affiliated Hexian Mem Hosp Dept Lab Med Guangzhou 511400 Guangdong Peoples R China

Pseudomonas aeruginosa is an important gram-negative pathogen that often causes skin, respiratory, and bloodstream infections. The virulence of P. aeruginosa is regulated by srnas through a complex network, which is still incompletely understood. This study employed transcriptome sequencing (rna-Seq) to screen srna 111, and real-time quantitative PCR was conducted for validation. In addition, an overexpression strain of srna111 was constructed and the effects of overexpression of srna111 on virulence factors such as biofilm formation, pyocyanin, swarming motility, inflammatory factors, and biofilm-associated factors were analyzed. The results revealed that srna111 might be closely related to the formation of P. aeruginosa biofilm. Compared to the vector, srna111 was found to enhance P. aeruginosa biofilm formation while also suppressing swarming motility, invasive ability, and adhesion capability. Meanwhile, srna111 up-regulated the expression of biofilm-related genes, such as Anr, pel family, polB, recA, etc., more significantly in the biofilm environment compared with the wild strain. In addition, srna111 effectively promoted the expression of inflammatory factors in the biofilm environment compared with the planktonic environment. These results implied that srna111 regulates the formation of P. aeruginosa biofilm and other virulence factors and further modulates the process of infection immunity.

关键词： Pseudomonas aeruginosa non-coding rna Small rna Virulence factors Biofilm Cytokines

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The Small non-coding Vault rna1-1 Acts as a Riboregulator of Autophagy

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CELL 2019年第5期176卷 1054-+页

作者： Horos, Rastislav Buescher, Magdalena Kleinendorst, Rozemarijn Alleaume, Anne-Marie Tarafder, Abul K. Schwarzl, Thomas Dziuba, Dmytro Tischer, Christian Zielonka, Elisabeth M. Adak, Asli Castello, Alfredo Huber, Wolfgang Sachse, Carsten Hentze, Matthias W. European Mol Biol Lab Meyerhofstr 1 D-69117 Heidelberg Germany Univ Oxford Dept Biochem South Parks Rd Oxford OX1 3QU England Ernst Ruska Ctr Microscopy & Spect Electrons ER C Wilhem Johnen Str D-52425 Julich Germany

Vault rnas (vtrna) are small non-coding rnas transcribed by rna polymerase III found in many eukaryotes. Although they have been linked to drug resistance, apoptosis, and viral replication, their molecular functions remain unclear. Here, we show that vault rnas directly bind the autophagy receptor sequestosome-1/p62 in human and murine cells. Overexpression of human vtrna1-1 inhibits, while its antisense LNA-mediated knockdown enhances p62-dependent autophagy. Starvation of cells reduces the steady-state and p62-bound levels of vault rna1-1 and induces autophagy. Mechanistically, p62 mutants that fail to bind vtrnas display increased p62 homo-oligomerization and augmented interaction with autophagic effectors. Thus, vtrna1-1 directly regulates selective autophagy by binding p62 and interference with oligomerization, a critical step of p62 function. Our data uncover a striking example of the potential of rna to control protein functions directly, as previously recognized for protein-protein interactions and post-translational modifications.

关键词： vault rna autophagy p62 sequestosome-1 vtrna1-1 vtrna starvation non-coding rna SQSTM1

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non-coding 7S rna inhibits transcription via mitochondrial rna polymerase dimerization

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CELL 2022年第13期185卷 2309-+页

作者： Zhu, Xuefeng Xie, Xie Das, Hrishikesh Tan, Benedict G. Shi, Yonghong Al-Behadili, Ali Peter, Bradley Motori, Elisa Valenzuela, Sebastian Posse, Viktor Gustafsson, Claes M. Haellberg, B. Martin Falkenberg, Maria Univ Gothenburg Dept Med Biochem & Cell Biol POB 440 S-40530 Gothenburg Sweden Karolinska Inst Dept Cell & Mol Biol S-17177 Stockholm Sweden Cologne Excellence Cluster Cellular Stress Respon D-50931 Cologne Germany Univ Cologne Inst Biochem Zulpicher Str 47 D-50674 Cologne Germany

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding rna molecule known as 7S rna is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S rna has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S rna. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S rna molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.

关键词： mitochondria transcription POLRMT 7S rna SUV3 dimer cryo-EM mtDNA mtEXO non-coding rna

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