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The circular rna circATP8B(2) regulates ROS production and antiviral immunity in Drosophila

CELL REPORTS 2024年第4期43卷 113973页

作者： Liang, Weihong Liu, Wei Xiong, Xiao-Peng Li, Jennifer W. Li, Jian-Liang Perera, Ranjan J. Zhou, Rui Johns Hopkins Univ Sch Med Dept Med Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Biol Chem Baltimore MD 21205 USA Johns Hopkins Univ Sch Med Dept Oncol Baltimore MD 21205 USA Johns Hopkins All Childrens Hosp St Petersburg FL 33701 USA Sanford Burnham Prebys Med Discovery Inst La Jolla CA 92037 USA Brown Univ Dept Med Providence RI 02912 USA Natl Inst Environm Hlth Sci Durham NC 27709 USA

We identified and validated a collection of circular rnas (circrnas) in Drosophila melanogaster . We show that depletion of the pro -viral circrna circATP8B(2) , but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo . In addition, circATP8B(2) is enriched in the fly gut, and gut -specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase ( Duox ), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2) -depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2) -Duox interaction is crucial for circATP8B(2) -mediated modulation of Duox activity. In addition, Gaq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2) . We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production.

关键词： circATP8B(2) circular rna antiviral immunity ROS Duox non-coding rna Drosophila

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CRISPR-Cas9 screens reveal common essential mirnas in human cancer cell lines

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GENOME MEDICINE 2024年第1期16卷 82-82页

作者： Merk, Daniel J. Paul, Linda Tsiami, Foteini Hohenthanner, Helen Kouchesfahani, Ghazal Mohseni Haeusser, Lara A. Walter, Bianca Brown, Adam Persky, Nicole S. Root, David E. Tabatabai, Ghazaleh Eberhard Karls Univ Tubingen Univ Hosp Tubingen Hertie Inst Clin Brain Res Dept Neurol & Interdisciplinary Neurooncol D-72076 Tubingen Germany Broad Inst MIT & Harvard Genet Perturbat Platform Cambridge MA 02142 USA Eberhard Karls Univ Tubingen Cluster Excellence iFIT EXC 2180 Image Guided & Fu D-72076 Tubingen Germany German Canc Res Ctr German Consortium Translat Canc Res DKTK Partner Site Tubingen D-69120 Heidelberg Germany Eberhard Karls Univ Tubingen Univ Hosp Tubingen Comprehens Canc Ctr Tubingen Stuttgart D-72076 Tubingen Germany

Background Genome-wide functional screening using the CRISPR-Cas9 system is a powerful tool to uncover tumor-specific and common genetic dependencies across cancer cell lines. Current CRISPR-Cas9 knockout libraries, however, primarily target protein-coding genes. This limits functional genomics-based investigations of mirna *** We designed a novel CRISPR-Cas9 knockout library (lentiG-miR) of 8107 distinct sgrnas targeting a total of 1769 human mirnas and benchmarked its single guide rna (sgrna) composition, predicted on- and off-target activity, and screening performance against previous libraries. Using a total of 45 human cancer cell lines, representing 16 different tumor entities, we performed negative selection screens to identify mirna fitness genes. Fitness mirnas in each cell line were scored using a combination of supervised and unsupervised essentiality classifiers. Common essential mirnas across distinct cancer cell lines were determined using the 90th percentile method. For subsequent validation, we performed knockout experiments for selected common essential mirnas in distinct cancer cell lines and gene expression *** We found significantly lower off-target activity for protein-coding genes and a higher mirna gene coverage for lentiG-miR as compared to previously described mirna-targeting libraries, while preserving high on-target activity. A minor fraction of mirnas displayed robust depletion of targeting sgrnas, and we observed a high level of consistency between redundant sgrnas targeting the same mirna gene. Across 45 human cancer cell lines, only 217 (12%) of all targeted human mirnas scored as a fitness gene in at least one model, and fitness effects for most mirnas were confined to small subsets of cell lines. In contrast, we identified 49 common essential mirnas with a homogenous fitness profile across the vast majority of all cell lines. Transcriptional profiling verified highly consistent gene expression changes in re

关键词： CRISPR-Cas9 knockout non-coding rna mirna Common essentiality Negative selection screens Functional annotation

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Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer

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MOLECULAR THERAPY 2021年第2期29卷 587-596页

作者： Luo, Xiao-Jing Zhao, Qi Liu, Jia Zheng, Jia-Bo Qiu, Miao-Zhen Ju, Huai-Qiang Xu, Rui-Hua Sun Yat Sen Univ Collaborat Innovat Ctr Canc Med State Key Lab Oncol South China Canc Ctr 651 Dongfeng East Rd Guangzhou 510060 Peoples R China

The therapeutic strategies of stage II/III colorectal cancer (CRC) patients after curative surgery remain controversial. In the clinical decision-making process, oncologists need to answer questions such as whether adjuvant chemotherapy is necessary or which therapeutic regimen should be given to each patient. At present, whether adjuvant chemotherapy should be applied is primarily based on histopathological features and clinical risk factors. However, only a fraction of patients can benefit from it. More rigorous stratifying biomarkers are urgently needed to help further distinguishing these populations of patients. Recent progress in next-generation sequencing and high-throughput technologies has greatly promoted biomarker discovery as well as our understanding of the underlying mechanisms in CRC. Novel genetic and epigenetic biomarkers that are associated with prognosis or therapeutic responses have emerged. In this review, we discuss the strategies of biomarker discovery and summarize the status and assess the utility of previously published biomarkers in CRC.Y

关键词： colorectal cancer biomarker prognostic predictive genomic transcriptomic epigenetic non-coding rna lncrna mirna circrna

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Global research states and trends of micro rna in irritable bowel syndrome: a bibliometric analysis

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CLINICAL AND EXPERIMENTAL MEDICINE 2024年第1期24卷 149-149页

作者： Chen, Hongxiu Xu, Zhifang Zhao, Honggang Cao, Jiazhen Wang, Rui He, Jing Nie, Ru Jia, Jialin Yuan, Shuting Li, Yonghong Liu, Zhicheng Zhang, Xinyu Ha, Lijuan Xu, Xiaoru Li, Tie Changchun Univ Chinese Med Coll Acupuncture & Tuina 1035 Boshuo Rd Changchun 130117 Peoples R China Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu 10 Poyang Lake Rd Tianjin 301617 Peoples R China Tianjin Univ Tradit Chinese Med Res Ctr Expt Acupuncture Sci 10 Poyang Lake Rd Tianjin 301617 Peoples R China Shenzhen Hosp Integrated Chinese & Western Med 528 Xinsha RdShajing St Shenzhen Peoples R China

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. non-coding rnas (ncrnas), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People's Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncrnas regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microrna (mirnas) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncrna may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncrnas (especially mirnas). Our findings will help understand the role of ncrnas in IBS and provide guidance to future studies.

关键词： Irritable bowel syndrome non-coding rna Global research Bibliometric microrna

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Potential molecular mechanisms and clinical implications of pirnas in preeclampsia: a review

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REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY 2024年第1期22卷 73页

作者： Ma, Yuanxuan Hou, Bo Zong, Jinbao Liu, Shiguo Qingdao Univ Affiliated Hosp Prenatal Diag Ctr Qingdao 266003 Shandong Peoples R China Qingdao Univ Affiliated Hosp Dept Med Genet Qingdao 266003 Shandong Peoples R China Qingdao Univ Affiliated Hosp Dept Cardiol Qingdao 266003 Shandong Peoples R China Qingdao Univ Oingdao Tradit Chinese Med Hosp Qingdao Hiser Hosp Dept Lab 4 Renmin Rd Qingdao 266033 Peoples R China Qingdao Univ Affiliated Hosp Med Genet Dept 16 Jiangsu Rd Qingdao 266003 Peoples R China

Preeclampsia is a multisystem progressive condition and is one of the most serious complications of pregnancy. Owing to its unclear pathogenesis, there are no precise and effective therapeutic targets for preeclampsia, and the only available treatment strategy is to terminate the pregnancy and eliminate the clinical symptoms. In recent years, non-coding rnas have become a hotspot in preeclampsia research and have shown promise as effective biomarkers for the early diagnosis of preeclampsia over conventional biochemical markers. PIWI-interacting rnas, novel small non-coding rna that interact with PIWI proteins, are involved in the pathogenesis of various diseases at the transcriptional or post-transcriptional level. However, the mechanisms underlying the role of PIWI-interacting rnas in the pathogenesis of preeclampsia remain unclear. In this review, we discuss the findings of existing studies on PIWI-interacting rna biogenesis, functions, and their possible roles in preeclampsia, providing novel insights into the potential application of PIWI-interacting rnas in the early diagnosis and clinical treatment of preeclampsia.

关键词： non-coding rna PIWI-interacting rna Preeclampsia Pregnancy Targeted therapy Biomarker Epigenomics

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Serum vault rna1-1 levels reflect blood cells and bone marrow

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MOLECULAR AND CELLULAR PROBES 2025年 80卷 102018页

作者： Hatayama, Yuki Shimohiro, Hisashi Hashimoto, Yuki Ichikawa, Hitomi Kawamura, Koji Motokura, Toru Tottori Univ Hosp Div Clin Lab Yonago Tottori Japan Tottori Univ Fac Med Sch Hlth Sci Dept Pathobiol Sci & Technol Yonago Tottori Japan Tsuyama Dai Ichi Hosp Tsuyama Japan

Introduction: Vault rna1-1 (vtrna1-1) exhibits antiviral and anti-apoptotic effects in infected and malignant cells. We observed that vtrna1-1 levels in serum fluctuate in patients with hematological disorders, but its extracellular functions remain unclear. This study evaluates the potential of serum vtrna1-1 levels as a biomarker for hematological disorders and investigates its association with bone marrow cell density (BMC). Methods: Blood and serum samples were collected from patients with hematological disorders, patients who underwent bone marrow examination, PBSCT donors, and AML patients who received chemotherapy. Vtrna1-1 levels were measured using real-time quantitative RT-PCR. BMC was calculated by digital image analysis, and multiple regression analysis was performed using serum vtrna1-1 and hematological and biochemical data as explanatory variables. Results: The vtrna1-1 levels in the blood of 11 patients with hematological disorders averaged 10.8 log10 cps/ml, significantly higher than 8.4 log10 cps/ml in serum. Multiple regression analysis estimated the vtrna1-1 expression levels of each blood cell. In 87 patients who underwent bone marrow examination, there was a significant correlation between serum vtrna1-1 levels and BMC (Rs = 0.24, P = 0.023). In PBSCT donors, serum vtrna1-1 levels increased after G-CSF administration (P < 0.001), and in AML patients, serum vtrna1-1 levels decreased after the initiation of chemotherapy, fluctuating in parallel with white blood cell counts. Conclusions: Our findings suggest that serum vtrna1-1, derived from peripheral blood and bone marrow cells, can potentially serve as a clinical biomarker in specific diseases.

关键词： Vault vtrna1-1 non-coding rna Extracellular vesicle Bone marrow cellularity

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Microrna Transcriptomes Reveal Prevalence of Rare and Species-Specific Arm Switching Events During Zebrafish Ontogenesis

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EVOLUTIONARY BIOINFORMATICS 2024年 20卷

作者： de Oliveira, Arthur Casulli Bovolenta, Luiz Augusto Figueiredo, Lucas Ribeiro, Amanda De Oliveira Pereira, Beatriz Jacinto Alves de Almeida, Talita Roberto Aleixo Campos, Vinicius Farias Patton, James G. Pinhal, Danillo Sao Paulo State Univ UNESP Inst Biosci Botucatu Dept Chem & Biol Sci Botucatu SP Brazil Sao Paulo State Univ UNESP Inst Biosci Dept Struct & Funct Biol Botucatu SP Brazil Univ Fed Pelotas Ctr Technol Dev Postgrad Program Biotechnol Lab Struct Genom Pelotas Rio Grande do S Brazil Vanderbilt Univ Dept Biol Sci Nashville TN USA

In metazoans, micrornas (mirnas) are essential regulators of gene expression, affecting critical cellular processes from differentiation and proliferation, to homeostasis. During mirna biogenesis, the mirna strand that loads onto the rna-induced Silencing Complex (RISC) can vary, leading to changes in gene targeting and modulation of biological pathways. To investigate the impact of these "arm switching" events on gene regulation, we analyzed a diverse range of tissues and developmental stages in zebrafish by comparing 5p and 3p arms accumulation dynamics between embryonic developmental stages, adult tissues, and sexes. We also compared variable arm usage patterns observed in zebrafish to other vertebrates including arm switching data from fish, birds, and mammals. Our comprehensive analysis revealed that variable arm usage events predominantly take place during embryonic development. It is also noteworthy that isomiR occurrence correlates to changes in arm selection evidencing an important role of microrna distinct isoforms in reinforcing and modifying gene regulation by promoting dynamics switches on mirna 5p and 3p arms accumulation. Our results shed new light on the emergence and coordination of gene expression regulation and pave the way for future investigations in this field.

关键词： microrna non-coding rna arm usage isomiRs gene regulation

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A comprehensive epigenetic network can influence the occurrence of thyroid-associated ophthalmopathy by affecting immune and inflammatory response

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SCIENTIFIC REPORTS 2024年第1期14卷 1-11页

作者： Zhang, Zhuo Wu, Hongshi Gong, Xun Yan, Yuerong Li, Xiaohui Yang, Rongxue Wu, Muchao Xu, Mingtong Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Endocrinol Guangzhou Peoples R China

The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncrna/circrna/mrna sequencing data, as well as several rna methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding rna, and rna methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding rna. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by rna epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.

关键词： Thyroid-associated ophthalmopathy DNA methylation non-coding rna rna methylation Immune and inflammatory response

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Advancements in small interfering rnas therapy for acute lymphoblastic leukemia: promising results and future perspectives

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MOLECULAR BIOLOGY REPORTS 2024年第1期51卷 737-737页

作者： Rastgar, Amirhossein Kheyrandish, Setare Vahidi, Mahmoud Heidari, Reza Ghorbani, Mahdi AJA Univ Med Sci Student Res Comm Fac Paramed Tehran Iran Tarbiat Modares Univ Fac Med Sci Dept Hematol & Blood Banking Tehran Iran Shahid Beheshti Univ Med Sci Student Res Comm Sch Allied Med Sci Dept Hematol & Blood Banking Tehran Iran Aja Univ Med Sci Fac Paramed Dept Med Lab Sci Tehran Iran Aja Univ Med Sci Canc Epidemiol Res Ctr Tehran Iran Aja Univ Med Sci Fac Paramed Dept Hematol Lab Sci Tehran Iran AJA Univ Med Sci Infect Dis Res Ctr Tehran Iran

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children, presenting significant healthcare challenges for some patients, including drug resistance and the need for targeted therapies. Sirna-based therapy is one potential solution, but problems can arise in administration and the need for a delivery system to protect sirna during intravenous injection. Additionally, sirna encounters instability and degradation in the reticuloendothelial system, off-target effects, and potential immune system stimulation. Despite these limitations, some promising results about sirna therapy in ALL patients have been published in recent years, showing the potential for more effective and precise treatment, reduced side effects, and personalized approaches. While sirna-based therapies demonstrate safety and efficacy, addressing the mentioned limitations is crucial for further optimization. Advancements in sirna-delivery technologies and combination therapies hold promise to improve treatment effectiveness and overcome drug resistance. Ultimately, despite its challenges, sirna therapy has the potential to revolutionize ALL treatments and improve patient outcomes.

关键词： sirna Small interfering rna non-coding rna Leukemia ALL Drug resistance

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Exploration and validation of cerna regulatory networks in colorectal cancer based on associations whole transcriptome sequencing

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SCIENTIFIC REPORTS 2024年第1期14卷 1-17页

作者： Zhang, Lulu Li, Yulei Fu, Chao Yang, Lixia Li, Gang Wu, Yiyang Tong, Huanjun Tian, Guojiang Wang, Kaifang Wang, Jun Ying, Xiaojiang Li, Zhenjun Shaoxing Peoples Hosp Med Res Ctr 568 Zhongxing North Rd Shaoxing 312000 Zhejiang Peoples R China Shaoxing Peoples Hosp 568 Zhongxing North Rd Shaoxing 312000 Zhejiang Peoples R China Shaoxing Peoples Hosp Dept Colorectal & Anal Surg 568 Zhongxing North Rd Shaoxing 312000 Zhejiang Peoples R China Univ Macau Fac Hlth Sci Ave Univ Taipa Macau Peoples R China

Colorectal cancer (CRC) is a wide-spread gastrointestinal cancer that is associated with augmented morbidity and mortality, and we do not yet have a deep understanding of its epidemiology and carcinogenicity. The transcriptome can reveal the complexity and heterogeneity of tumors and uncover new biomarkers or treatment options. In this study, we identified messenger rnas (mrnas), long non-coding rnas (lncrnas), round rnas (circrnas), and micrornas (mirnas) using whole-transcriptome sequencing and generated competing endogenous rna (cerna) modulatory axes. We conducted whole transcriptome sequencing on 10 CRC and para-cancer (CRCP) samples and discovered 2465 differentially expressed (DE) mrnas (DEmrnas), 77 DE mirnas (DEmirnas). 2852 DE lncrnas (DElncrnas) and 1477 DE circrnas (DEcircrnas). In addition, utilizing co-DE analysis, we generated the cerna axis. Subsequently, we employed the cerna axis to identify essential genes and corresponding associations with lncrnas, circrnas, and mirnas in CRC. cerna regulatory network including mrna-mirna-lncrna and mrna-mirna-circrna. These modulatory axes potentially modulate the positive regulation of smooth muscle contraction, melanosome, plasma membrane, integral plasma membrane component and so on. Finally, the results of rna sequencing (rna-SEQ) were combined with the TCGA and GEO databases, and the DEGs strongly correlated with the TCGA-COAD overall survival (OS) as estimated by univariate cox and logarithmic rank analyses were cross-analyzed, and the co-upregulated DEGs were screened. Among the many DEs, KPNA2 was chosen for additional analysis. Using invitro experimentations, western blot, CCK8, EdU and other experiments were performed to verify the results. We found sirna-based KPNA2 depletion reduces bladder cancer cells' viability, migratory, and proliferative activities, which showed that the DEmrna profiles were comparable to the sequencing information, confirming that the sequencing data were very reliable. These

关键词： CRC Whole transcriptome Competing endogenous rna non-coding rna Expression pattern

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