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Crosstalk between rna m⁶A Modification and non-coding rna Contributes to Cancer Growth and Progression

MOLECULAR THERAPY NUCLEIC ACIDS 2020年 22卷 62-71页

作者： Dai, Fengsheng Wu, Yongyan Lu, Yan An, Changming Zheng, Xiwang Dai, Li Guo, Yujia Zhang, Linshi Li, Huizheng Xu, Wei Gao, Wei Shanxi Med Univ Hosp 1 Shanxi Key Lab Otorhinolaryngol Head & Neck Canc Taiyuan 030001 Peoples R China Shanxi Med Univ Hosp 1 Shanxi Prov Clin Med Res Ctr Precis Med Head & Ne Taiyuan 030001 Peoples R China Shanxi Med Univ Hosp 1 Dept Otolaryngol Head & Neck Surg Taiyuan 030001 Peoples R China Shanxi Med Univ Minist Educ Key Lab Cellular Physiol Taiyuan 030001 Peoples R China Jinzhou Med Univ Hosp 1 Dept Otolaryngol Head & Neck Surg Jinzhou 121001 Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Natl Canc Ctr Canc Hosp Dept Head & Neck Surg Beijing 100021 Peoples R China Zhejiang Univ Affiliated Hosp 2 Dept Thyroid Surg Hangzhou 310009 Peoples R China Dalian Med Univ Dalian Municipal Friendship Hosp Dept Otolaryngol Head & Neck Surg Dalian 116100 Peoples R China Shandong Univ Shandong Prov ENT Hosp Dept Head & Neck Surg Jinan 250022 Peoples R China Shandong Prov Inst Otolaryngol Jinan 250022 Peoples R China Shandong Univ Minist Hlth Key Lab Otolaryngol Jinan 250022 Peoples R China

N6-methyladenosine (m(6)A) is the most common rna modification and has an important role in normal development and tumorigenesis. The abnormal expression of m6A regulators can lead to an imbalance in m(6)A levels in cancer cells, leading to the dysregulated expression of oncogenes and tumor suppressor genes that may contribute to cancer development, patient response to chemoradiotherapy, and clinical prognosis. Recent studies demonstrate that non-coding rnas are involved in epigenetic modification of both DNA and rna in tumor cells, and may also affect the development and progression of cancer by targeting m(6)A regulators. In this review, we describe the functional crosstalk between m(6)A and non-coding rnas, particularly microrna, long non-coding rna, and circular rna, and illustrate their roles in tumor regulation. Finally, we discuss the significance of non-coding rna and m(6)A modification in the diagnosis, treatment, and prognosis of cancer patients, as well as potential future research directions.

关键词： cancer N6-methyladenosine non-coding rna microrna long non-coding rna circular rna

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Small non-coding rna and cancer

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CARCINOGENESIS 2017年第5期38卷 485-491页

作者： Romano, Giulia Veneziano, Dario Acunzo, Mario Croce, Carlo M. Ohio State Univ Dept Canc Biol & Genet Columbus OH 43210 USA

The ENCODE project has reported that at least 80% of the human genome is biologically active, yet only a small part of human DNA encodes for protein. The massive amount of rna transcribed but not translated into protein can be classified as housekeeping rna (such as rrna, trna) and regulatory rna (such as mirna, pirna, lncrna). Small non-coding rnas, in particular, have been the focus of many studies in the last 20 years and their fundamental role in many human diseases is currently well established. Inter alia, their role in cancer development and progression, as well as in drug resistance, is being increasingly investigated. In this review, focusing our attention on recent research results, we provide an overview of the four large classes of small non-coding rnas, namely, mirnas, pirnas, snorna and the new class of trna-derived fragments, highlighting their fundamental role in cancer and their potential as diagnostic and prognostic biomarkers.

关键词： HUMAN genome DNA non-coding rna rna DISEASES

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In Vivo Cleavage Map Illuminates the Central Role of rnase E in coding and non-coding rna Pathways

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MOLECULAR CELL 2017年第1期65卷 39-51页

作者： Chao, Yanjie Li, Lei Girodat, Dylan Foerstner, Konrad U. Said, Nelly Corcoran, Colin Smiga, Michal Papenfort, Kai Reinhardt, Richard Wieden, Hans-Joachim Luisi, Ben F. Vogel, Joerg Univ Wurzburg Inst Mol Infect Biol D-97080 Wurzburg Germany Univ Wurzburg Core Unit Syst Med D-97080 Wurzburg Germany Univ Lethbridge Dept Chem & Biochem Alberta RNA Res & Training Inst Lethbridge AB T1K 3M4 Canada Free Univ Berlin Lab Struct Biochem Berlin Germany Ludwig Maximilians Univ Munchen Microbiol Dept Biol 1 D-82152 Martinsried Germany Max Planck Inst Plant Breeding Res Max Planck Genome Ctr Cologne D-50829 Cologne Germany Univ Cambridge Dept Biochem Cambridge CB2 1GA England Helmholtz Inst RNA Based Infect Res HIRI D-97080 Wurzburg Germany

Understanding rna processing and turnover requires knowledge of cleavages by major endoribonucleases within a living cell. We have employed TIER-seq (transiently inactivating an endoribonuclease followed by rna-seq) to profile cleavage products of the essential endoribonuclease rnase E in Salmonella enterica. A dominating cleavage signature is the location of a uridine two nucleotides downstream in a single-stranded segment, which we rationalize structurally as a key recognition determinant that may favor rnase E catalysis. Our results suggest a prominent biogenesis pathway for bacterial regulatory small rnas whereby rnase E acts together with the rna chaperone Hfq to liberate stable 30 fragments from various precursor rnas. Recapitulating this process in vitro, Hfq guides rnase E cleavage of a representative small-rna precursor for interaction with a mrna target. In vivo, the processing is required for target regulation. Our findings reveal a general maturation mechanism for a major class of post-transcriptional regulators.

关键词： rnase E rna degradome non-coding rna Hfq 3′ UTR ArcZ RprA srna maturation uridine ruler TIER-seq

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The signaling pathways involved in non-coding rna regulation during osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis

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JOUrnaL OF PERIODONTAL RESEARCH 2024年第1期59卷 18-31页

作者： Zhu, Yinci Guan, Xiaoyan Geng, Xiaorui Du, Yuanhang Jin, Suhan Liu, Jianguo Zunyi Med Univ Sch Stomatol Zunyi Peoples R China Zunyi Med Univ Affiliated Stomatol Hosp Dept Orthodont Zunyi Peoples R China Longgang ENT Hosp Dept Otolaryngol Shenzhen Peoples R China Inst ENT Shenzhen Shenzhen Key Lab ENT Shenzhen Peoples R China Higher Educ Inst Special Key Lab Oral Dis Res Zunyi Peoples R China Zunyi Med Univ Higher Educ Inst Sch Stomatol Special Key Lab Oral Dis Res Zunyi Peoples R China

Periodontitis is a prevalent oral disease caused by chronic inflammation of the periodontal tissues surrounding the teeth, which can lead to bone loss, tooth loosening, and even tooth loss. This inflammation has a negative impact on the osteogenic differentiation capacity of periodontal tissue-derived cells. non-coding rnas (ncrnas) are a class of rna molecules that do not encode proteins but can regulate various physiological processes. In this review, we summarized the critical signaling pathways that ncrnas modulate in osteogenic differentiation of periodontal tissue-derived cells, such as the Wnt, BMP/Smad, NF-kappa B, and PI3-K/Akt/mTOR pathways. This comprehensive exploration of ncrna-mediated modulation offers fresh and promising insights for prospective approaches in the management of periodontitis and the advancement of periodontal regeneration therapies.

关键词： non-coding rna osteogenic differentiation periodontal tissue-derived cells periodontitis signaling pathway

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Extracellular vesicles and their non-coding rna cargos: Emerging players in cardiovascular disease

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JOUrnaL OF PHYSIOLOGY-LONDON 2023年第22期601卷 4989-5009页

作者： Collado, Aida Gan, Lu Tengbom, John Kontidou, Eftychia Pernow, John Zhou, Zhichao Karolinska Inst Dept Med Solna Div Cardiol Stockholm Sweden Sichuan Univ West China Hosp Dept Emergency Med Lab Emergency Med Chengdu Peoples R China Karolinska Univ Hosp Dept Cardiol Stockholm Sweden

Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, have recently received attention as essential mechanisms for cell-to-cell communication in cardiovascular disease. EVs can be released from different types of cells, including endothelial cells, smooth muscle cells, cardiac cells, fibroblasts, platelets, adipocytes, immune cells and stem cells. non-coding (nc)rnas as EV cargos have recently been investigated in the cardiovascular system. Up- or downregulated ncrnas in EVs have been shown to play a crucial role in various cardiovascular diseases. Communication via EV-derived ncrnas can occur between cells of the same type and between different types of cells involved in the pathophysiology of cardiovascular disease. In the present review, we highlight the important aspects of diverse cell-derived EVs and their ncrna cargos as disease mediators and potential therapeutic targets in atherosclerosis, coronary artery disease, ischaemic heart disease and cardiac fibrosis. In addition, we summarize the potential of EV-derived ncrnas in the treatment of cardiovascular disease. Finally, we discuss the different methods for EV isolation and characterization. A better understanding of the specific role of EVs and their ncrna cargos in the regulation of cardiovascular (dys)function will be of importance for the development of diagnostic and therapeutic tools for cardiovascular disease.

关键词： cardiovascular disease extracellular vesicles non-coding rna therapy

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Whole transcriptome analysis to identify non-coding rna regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell rna sequencing, weighted gene co-expression network analysis, and mrna-mirna-lncrna interaction analysis

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BMC GENOMICS 2024年第1期25卷 1页

作者： Karoii, Danial Hashemi Azizi, Hossein Skutella, Thomas Univ Tehran Coll Sci Sch Biol Dept Cell & Mol Biol Tehran Iran Amol Univ Special Modern Technol Fac Biotechnol Amol Iran Heidelberg Univ Inst Anat & Cell Biol Med Fac Neuenheimer Feld 307 D-69120 Heidelberg Germany

Background The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation of non-coding rna (ncrna), crucial for sperm development, are significant factors. This gene expression can affect sperm motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in sperm differentiation and development is vital. This knowledge could lead to more effective treatments and interventions for male *** and methods Our research aim to identify new and key genes and ncrna involved in non-obstructive azoospermia (NOA), improving genetic diagnosis and offering more accurate estimates for successful sperm extraction based on an individual's *** We analyzed the transcript of three NOA patients who tested negative for genetic sperm issues, employing comprehensive genome-wide analysis of approximately 50,000 transcript sequences using microarray technology. This compared gene expression profiles between NOA sperm and normal sperm. We found significant gene expression differences: 150 genes were up-regulated, and 78 genes were down-regulated, along with 24 ncrnas up-regulated and 13 ncrnas down-regulated compared to normal conditions. By cross-referencing our results with a single-cell genomics database, we identified overexpressed biological process terms in differentially expressed genes, such as "protein localization to endosomes" and "xenobiotic transport." Overrepresented molecular function terms in up-regulated genes included "voltage-gated calcium channel activity," "growth hormone-releasing hormone receptor activity," and "sialic acid transmembrane transporter activity." Analysis revealed nine hub genes associated with NOA sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1, and *** These genes and their interacting proteins may play a role in the pathophysiology of germ cell abnormalities

关键词： Sperm non-coding rna Infertility Genes expression non-obstructive azoospermia Single-cell

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NrsZ: a novel, processed, nitrogen-dependent, small non-coding rna that regulates Pseudomonas aeruginosa PAO1 virulence

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ENVIRONMENTAL MICROBIOLOGY 2014年第4期16卷 1053-1068页

作者： Wenner, Nicolas Maes, Alexandre Cotado-Sampayo, Marta Lapouge, Karine Univ Lausanne Dept Fundamental Microbiol CH-1015 Lausanne Switzerland Fasteris SA CH-1228 Plan Les Ouates Switzerland

The opportunistic pathogen Pseudomonas aeruginosa PAO1 has a remarkable capacity to adapt to various environments and to survive with limited nutrients. Here, we report the discovery and characterization of a novel small non-coding rna: NrsZ (nitrogen-regulated srna). We show that under nitrogen limitation, NrsZ is induced by the NtrB/C two-component system, an important regulator of nitrogen assimilation and P. aeruginosa's swarming motility, in concert with the alternative sigma factor RpoN. Furthermore, we demonstrate that NrsZ modulates P. aeruginosa motility by controlling the production of rhamnolipid surfactants, virulence factors notably needed for swarming motility. This regulation takes place through the post-transcriptional control of rhlA, a gene essential for rhamnolipids synthesis. Interestingly, we also observed that NrsZ is processed in three similar short modules, and that the first short module encompassing the first 60 nucleotides is sufficient for NrsZ regulatory functions.

关键词： non-coding rna PSEUDOMONAS aeruginosa VIRULENCE (Microbiology) RHAMNOLIPIDS GLYCOLIPIDS BACTERIA -- Swarming

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Characteristics of long non-coding rna and its relation to hepatocellular carcinoma

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CARCINOGENESIS 2014年第3期35卷 507-514页

作者： Huang, Jin-Lan Zheng, Lei Hu, Yan-Wei Wang, Qian Southern Med Univ Nanfang Hosp Lab Med Ctr Guangzhou 510515 Guangdong Peoples R China

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high prevalence and lethality. However, the underlying mechanism for HCC has not been entirely elucidated. Recent studies have highlighted the roles of long non-coding rnas (lncrnas) in carcinogenesis, and it is suggested that they might play critical roles in HCC progression. Here, we will briefly introduce the biology of lncrnas, emphasizing the mechanisms and emerging roles of HCC-related lncrnas. To date, HCC-related lncrnas are demonstrated to influence the life cycle of genes by various means including epigenetic silencing, splicing regulation, lncrnamirna interaction, lncrnaprotein interaction and genetic variation. Moreover, they can participate in diverse biological processes involved in HCC progression through impacts upon cell proliferation, apoptosis, invasion and metastasis and angiogenesis. Since lncrna can present in body fluid and have good specificity and accessibility, some HCC-related lncrnas are suggested to be useful as novel potential biomarkers for HCC diagnosis, prognosis and prediction of response to therapy. Those HCC-related lncrnas may provide potential novel therapeutic targets for HCC and other diseases.

关键词： non-coding rna LIVER -- Cancer GENE silencing APOPTOSIS CELL proliferation EPIGENETICS

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A Long non-coding rna, LncMyoD, Regulates Skeletal Muscle Differentiation by Blocking IMP2-Mediated mrna Translation

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DEVELOPMENTAL CELL 2015年第2期34卷 181-191页

作者： Gong, Chenguang Li, Zhizhong Ramanujan, Krishnan Clay, Ieuan Zhang, Yunyu Lemire-Brachat, Sophie Glass, David J. Novartis Inst Biomed Res Cambridge MA 02139 USA Novartis Inst Biomed Res CH-4002 Basel Switzerland

Increasing evidence suggests that long non-coding rnas (Lncrnas) represent a new class of regulators of stem cells. However, the roles of Lncrnas in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of intergenic Lncrnas were identified that are expressed in myoblasts and regulated during differentiation. One of these Lncrnas, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation, largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mrna-binding protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the rna sequence of LncMyoD is not well conserved between human and mouse, its locus, gene structure, and function are preserved. The MyoD-LncMyoDIMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.

关键词： non-coding rna SKELETAL muscle CELL differentiation GENETIC translation MESSENGER rna MYOGENESIS

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The non-coding rna world of the bacterial pathogen Listeria monocytogenes

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rna BIOLOGY 2012年第4期9卷 372-378页

作者： Mellin, Jeffrey R. Cossart, Pascale Inst Pasteur Unite Interact Bacteries Cellules Paris France INSERM U604 Paris France INRA USC2020 Paris France

In recent years, Listeria monocytogenes has emerged as a model organism in infection biology and also become an attractive system for the study of regulatory rnas in pathogenic bacteria. Due to the recent completion of several transcriptomic studies, it is now clear that L. monocytogenes possesses a large repertoire of both cis- and trans-encoded rnas. These include numerous small rnas (srnas) expressed during infection, widespread transcription of both short and long antisense rnas (asrnas) and an array of cis-acting regulatory rna elements. In this review we highlight the recent advances in non-coding rna research in L. monocytogenes with a particular focus on emerging themes of rna-based regulation.

关键词： srna asrna riboswitch non-coding rna ncrna transcriptomics rna-seq Hfq listeria

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