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The bioinformatics toolbox for circrna discovery and analysis

BRIEFINGS IN BIOINFORMATICS 2021年第2期22卷 1706-1728页

作者： Chen, Liang Wang, Changliang Sun, Huiyan Wang, Juexin Liang, Yanchun Wang, Yan Wong, Garry Shantou Univ Dept Comp Sci Key Lab Intelligent Mfg Technol Minist Educ Shantou Peoples R China Univ Macau Fac Hlth Sci Taipa Macao Peoples R China Jilin Univ Sch Artificial Intelligence Changchun Peoples R China Univ Missouri Dept Elect Engn & Comp Sci Columbia MO 65211 USA Univ Missouri Bond Life Sci Ctr Columbia MO 65211 USA Jilin Univ Coll Comp Sci & Technol Changchun Peoples R China Jilin Univ Sch Comp Sci Zhuhai Coll Changchun Peoples R China

Circular rnas (circrnas) are a unique class of rna molecule identified more than 40 years ago which are produced by a covalent linkage via back-splicing of linear rna. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field of types and biological functions of circrnas. In parallel with technological developments, practical applications of circrnas have arisen including their utilization as biomarkers of human disease. Currently, circrna-associated bioinformatics tools can support projects including circrna annotation, circrna identification and network analysis of competing endogenous rna (cerna). In this review, we collected about 100 circrna-associated bioinformatics tools and summarized their current attributes and capabilities. We also performed network analysis and text mining on circrna tool publications in order to reveal trends in their ongoing development.

关键词： circrna bioinformatics tools text mining next generation sequencing non-coding rna disease biomarker

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ncrna BC1 influences translation in the oocyte

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rna BIOLOGY 2021年第11期18卷 1893-1904页

作者： Aleshkina, D. Iyyappan, R. Lin, Ch. J. Masek, T. Pospisek, M. Susor, A. Czech Acad Sci Inst Anim Physiol & Genet Lab Biochem & Mol Biol Germ Cells Libechov Czech Republic Univ Edinburgh MRC Ctr Reprod Hlth Edinburgh Midlothian Scotland Charles Univ Prague Fac Sci Dept Genet & Microbiol Prague Czech Republic

Regulation of translation is essential for the diverse biological processes involved in development. Particularly, mammalian oocyte development requires the precisely controlled translation of maternal transcripts to coordinate meiotic and early embryo progression while transcription is silent. It has been recently reported that key components of mrna translation control are short and long noncoding rnas (ncrnas). We found that the ncrnaBrain cytoplasmic 1 (BC1) has a role in the fully grown germinal vesicle (GV) mouse oocyte, where is highly expressed in the cytoplasm associated with polysomes. Overexpression of BC1 in GV oocyte leads to a minute decrease in global translation with a significant reduction of specific mrna translation via interaction with the Fragile X Mental Retardation Protein (FMRP). BC1 performs a repressive role in translation only in the GV stage oocyte without forming FMRP or Poly(A) granules. In conclusion, BC1 acts as the translational repressor of specific mrnas in the GV stage via its binding to a subset of mrnas and physical interaction with FMRP. The results reported herein contribute to the understanding of the molecular mechanisms of developmental events connected with maternal mrna translation.

关键词： non-coding rna translation oocyte embryo development

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Rewiring of chromatin state and gene expression by transposable elements

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DEVELOPMENT GROWTH & DIFFERENTIATION 2021年第4-5期63卷 262-273页

作者： Ohtani, Hitoshi Iwasaki, Yuka W. Nagoya Univ Grad Sch Bioagr Sci Dept Anim Sci Lab Genome & Epigenome Dynam Nagoya Aichi Japan Keio Univ Sch Med Dept Mol Biol Tokyo 1608582 Japan Japan Sci & Technol Agcy JST Precursory Res Embryon Sci & Technol PRESTO Saitama Japan

Transposable elements form a major fraction of the genome in various eukaryotic species. Although deleterious effects of transpositions within the genome have been reported, recent findings suggest that transposable elements can function as novel regulatory elements to fine-tune gene expression. Transposable elements can impact the chromatin state through processes such as heterochromatin formation, enhancer-promoter interactions, and chromatin boundary formation, mainly because of the functions of chromatin-based pathways that regulate the expression of transposable elements via DNA methylation and repressive histone modification. Therefore, transposable elements can rewire the chromatin state and gene expression depending on their insertions. Here, we review the findings that reveal the role of transposable elements as modifiers of the chromatin state and gene expression as well as the molecular mechanisms capable of inducing these changes.

关键词： transposable element enhancer transcriptional regulation non-coding rna chromatin state

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The Emerging Clinical Application of m6A rna Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

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JOUrnaL OF INFLAMMATION RESEARCH 2021年 14卷 3289-3306页

作者： Xu, Xinwei Huang, Jintu Ocansey, Dickson Kofi Wiredu Xia, Yuxuan Zhao, Zihan Xu, Zhiwei Yan, Yongmin Zhang, Xu Mao, Fei Jiangsu Univ Dept Clin Lab Diagnost Key Lab Med Sci & Lab Med Jiangsu Prov Sch Med Zhenjiang 212013 Jiangsu Peoples R China Nantong Univ Clin Lab Dept Peoples Hosp Danyang Affiliated Danyang Hosp Zhenjiang 212300 Jiangsu Peoples R China Univ Cape Coast Dept Clin Lab Diagnost Directorate Univ Hlth Serv Cape Coast Ghana

Methylation, first proposed in DNAs, but later found in rnas, serves as one of the most widespread epigenetic modifications in eukaryotes, where N6-methyladenosine (m6A) modification has been found to play an important role in a variety of cancers including colorectal cancer (CRC). Under the action of various enzymes and proteins, the regulatory role of m6A in rnas and immune cells has also been gradually realized. This paper reviews the general biogenesis and effects of m6A, and its emerging crucial role in intestinal mucosal immunity via the regulation of rnas and immune cells, and thus closely related to the occurrence and development of inflammatory bowel disease (IBD) and CRC. m6A-related genes and regulatory factors are expected to be potential predictive markers and therapeutic targets.

关键词： N6-methyladenosine inflammatory bowel disease colorectal cancer non-coding rna intestinal mucosal immunity

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Exosomal circ_0084043 derived from colorectal cancer-associated fibroblasts promotes in vitro endothelial cell angiogenesis by regulating the miR-140-3p/HIF-1 α /VEGF signaling axis

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HELIYON 2024年第11期10卷 e31584页

作者： Payervand, Nafiseh Pakravan, Katayoon Razmara, Ehsan Vinu, Kailash Kumar Ghodsi, Sara Heshmati, Masoumeh Babashah, Sadegh Islamic Azad Univ Fac Adv Sci & Technol Dept Cellular & Mol Biol Tehran Med Sci Tehran Iran Tarbiat Modares Univ Fac Biol Sci Dept Mol Genet Tehran Iran Tarbiat Modares Univ Sch Med Sci Dept Med Genet Tehran Iran Monash Univ Australian Regenerat Med Inst Clayton Vic 3800 Australia

Background: Circular rnas (circrnas) hold potential as diagnostic markers for colorectal cancer (CRC);however, their functional mechanisms remain incompletely elucidated. This work investigates the clinical implications of a unique set comprising six circrnas derived from serum in CRC. Furthermore, we delve into the role of exosomal circ_0084043, originating from colorectal cancer -associated fibroblasts (CAFs), with a specific focus on its contribution to endothelial cell angiogenesis. Methods: The study analyzed circrna levels in serum samples obtained from both CRC and control groups using qRT-PCR. Additionally, exosomes originating from colorectal CAFs and normal fibroblasts (NFs) were purified and confirmed by electron microscopy and Western blotting techniques. The proangiogenic effects of CAF -derived exosomal circ_0084043 were assessed in endothelial cells through proliferation, migration, and in vitro capillary tube formation assays. Gain- and loss -of -function experiments were employed to clarify the role of the circ_0084043/miR-140 -3p/HIF-1 alpha axis in endothelial cell angiogenesis, utilizing luciferase reporter assay, Western blotting, and ELISA for mechanism elucidation. Results: The candidate circrnas (circ_0060745, circ_001569, circ_007142, circ_0084043, Circ_BANP, and CiRS-7) exhibited notably elevated expression in CRC patient sera compared to the levels observed in healthy individuals. Except for CiRS-7, all circrnas showed elevated expression in CRC patients with positive lymph node metastasis and advanced tumor stages. Exosomes released by colorectal CAFs augmented endothelial cell proliferation, migration, and angiogenesis by upregulating VEGF expression and secretion. Circ_0084043 was highly detected in endothelial cells treated with CAF -derived exosomes. Silencing circ_0084043 reduced VEGFA expression and diminished CAF exosome-induced endothelial cell processes, indicating its pivotal role in angiogenesis. Circ_0084043 sponges miR-140 -3

关键词： Colorectal cancer Cancer-associated fibroblasts Exosome non-coding rna Angiogenesis

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Changes of mrna, mirna and lncrna expression contributing to skeletal muscle differences between fetus and adult Mongolian horses

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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS 2024年 52卷 101294页

作者： Ding, Wenqi Gong, Wendian Liu, Huiying Hu, Hanwen Shi, Lin Ren, Xiujuan Cao, Yuying Zhang, Aaron Shi, Xiaoyuan Li, Zheng Bou, Tugeqin Dugarjaviin, Manglai Bai, Dongyi Inner Mongolia Agr Univ Coll Anim Sci Equus Res CtrMinist Agr & Rural AffairsKey Lab Inner Mongolia Key Lab Equine Sci Res & Technol In Hohhot 010018 Peoples R China

The growth and development of myofibers, as the fundamental units comprising muscle tissue, and their composition type are indeed among the most crucial factors influencing skeletal muscle types. Muscle fiber adaptation is closely associated with alterations in physiological conditions. Muscle fiber types undergo dynamic changes in fetus and adult horses. Our aim is to investigate the mechanisms influencing the differences in muscle fiber types between fetal and adult stages of Mongolian horses. The study investigated the distribution of muscle fiber types within longissimus dorsi muscle of fetus and adult Mongolian horses. A total of 652 differentially expressed genes (DEGs), 476 Differentially expressed lncrnas (DELs), and 174 Differentially expressed mirnas (DEMIRs) were identified using deep rna-seq analysis. The results of functional analysis reveal the transformations in muscle fiber type from the fetal to adult stage in Mongolian horses. The up-regulated DEGs were implicated in the development and differentiation of muscle fibers, while down-regulated DEGs were associated with muscle fiber contraction, transformation, and metabolism. Additionally, connections between non-coding rna and mrna landscapes were identified based on their functional alterations, some non-coding rna target genes may be associated with immunity. These data have broadened our understanding of the specific roles and interrelationships among regulatory molecules involved in Mongolian horse development, this provides new perspectives for selecting and breeding superior individuals and for disease prevention.

关键词： Mongolian horse Skeletal muscle non-coding rna Muscle development Muscle contraction

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Novel and deleterious nucleotide variations in the HAND1 gene probably affect mirna target sites and protein function in pediatric patients with congenital heart disease

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MOLECULAR BIOLOGY REPORTS 2024年第1期51卷 468-468页

作者： Tabrizi, Fateme Khatami, Mehri Heidari, Mohammad Mehdi Braganca, Jose Tatari, Hasan Namnabat, Mohsen Hadadzadeh, Mehdi Shirazi, Mohammad Ali Navabi Yazd Univ Dept Biol Yazd Iran Univ Algarve Algarve Biomed Ctr Res Inst ABC RI Fac Med & Biomed Sci Faro Portugal Iran Univ Med Sci Rajaie Cardiovasc Med & Res Ctr Tehran Iran Univ Copenhagen Fac Sci Dept Biol Copenhagen Denmark Shahid Sadoughi Univ Med Sci Afshar Hosp Dept Cardiac Surg Yazd Iran Univ Tehran Med Sci Childrens Med Ctr Dept Pediat Cardiac Surg Tehran 14194 Iran

Background: Congenital heart disease (CHD) is the most prevalent developmental defect and principal cause of infant mortality and affects cardiac and large blood vessel structures in approximately 1% of live births worldwide. To date, numerous studies have related critical genetic dysfunctions to the pathogenesis of CHDs. However, the genetic basis underlying CHD remains largely unknown. In the present study, we investigated the association of nucleotide variations in coding and noncoding regions of the HAND1 gene with the risk of CHD. The HAND1 gene, encoding a helix-loop-helix transcription factor, is particularly relevant for mechanisms underlying CHD since it plays a significant role in heart development. Methods and results: The genomic DNA of 150 unrelated pediatric patients with CHD was screened by PCR-SSCP and direct sequencing. Four novel and heterozygous missense mutations were identified in the first exon, with three causing amino acid substitutions (***149Met, ***142His, and ***146Met). In-silico analysis also indicated their deleterious impact on protein structure and function. In addition, we identified five novel nucleotide variants in the 3'UTR region (c.*461, c.*342, c.*529, c.*448, c.*593), potentially altering the target sites of mirnas. These changes include the loss of certain target sites and the acquisition of new ones. Conclusions: These findings confirm the phenotypic association between CHDs and HAND1 mutations and can pave the way for developing new preventive and therapeutic strategies.

关键词： Congenital heart disease Heart development non-coding rna 3'UTR HAND1

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A tumor microenvironment-related mrna-ncrna signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma

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JOUrnaL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 2021年第11期147卷 3195-3209页

作者： Gao, Zhendong Han, Han Zhao, Yue Yuan, Hui Zheng, Shanbo Zhang, Yang Chen, Haiquan Fudand Univ Shanghai Canc Ctr Dept Thorac Surg 270 Dong An Rd Shanghai 200032 Peoples R China Fudand Univ Shanghai Canc Ctr State Key Lab Genet Engn 270 Dong An Rd Shanghai 200032 Peoples R China Fudan Univ Inst Thorac Oncol Shanghai 200032 Peoples R China Fudan Univ Shanghai Med Coll Dept Oncol Shanghai 200032 Peoples R China

Objectives Postoperative early relapse of early-stage lung adenocarcinoma is implicated in poor prognosis. The purpose of our study was to develop an integrated mrna and non-coding rna (ncrna) signature to identify patients at high risk of early relapse in stage I-II lung adenocarcinoma who underwent complete resection. Methods Early-stage lung adenocarcinoma data from Gene Expression Omnibus database were divided into training set and testing set. Propensity score matching analysis was performed between patients in early relapse group and long-term nonrelapse group from training set. Transcriptome analysis, random survival forest and LASSO Cox regression model were used to build an early relapse-related multigene signature. The robustness of the signature was evaluated in testing set and rna-Seq dataset from The Cancer Genome Atlas (TCGA). The chemotherapy sensitivity, tumor microenvironment and mutation landscape related to the signature were explored using bioinformatics analysis. Results Twelve mrnas and one ncrna were selected. The multigene signature achieved a strong power for early relapse prediction in training set (HR 3.19, 95% CI 2.16-4.72, P < 0.001) and testing set (HR 2.91, 95% CI 1.63-5.20, P = 0.002). Decision curve analyses revealed that the signature had a good clinical usefulness. Groups divided by the signature exhibited different chemotherapy sensitivity, tumor microenvironment characteristics and mutation landscapes. Conclusions Our results indicated that the integrated mrna-ncrna signature may be an innovative biomarker to predict early relapse of early-stage lung adenocarcinoma, and may provide more effective treatment strategies.

关键词： non-coding rna mrna Lung adenocarcinoma Prognostic signature Early relapse

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Changes in liver microrna expression and their possible regulatory role in energy metabolism-related genes in hibernating black bears

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JOUrnaL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY 2021年第2期191卷 397-409页

作者： Nishida, Kazuhei Shimozuru, Michito Okamatsu-Ogura, Yuko Miyazaki, Mitsunori Soma, Tsukasa Sashika, Mariko Tsubota, Toshio Hokkaido Univ Fac Vet Med Lab Wildlife Biol & Med Kita Ku Kita 18 Nishi 9 Sapporo Hokkaido 0600818 Japan Hokkaido Univ Fac Vet Med Lab Biochem Kita Ku Kita 18 Nishi 9 Sapporo Hokkaido 0600818 Japan Hlth Sci Univ Hokkaido Sch Rehabil Sci Dept Phys Therapy Tobetsu Hokkaido 0610293 Japan

Hibernating bears survive up to 6 months without feeding while yet maintaining metabolic homeostasis. We previously reported expression changes in energy metabolism-related genes in the liver of hibernating Japanese black bears. The present study examined the role of micrornas in the regulation of hepatic gene expression during hibernation. The quantitative analyses revealed significant increases in the expression of 4 micrornas (miR-221-3p, miR-222-3p, miR-455-3p, and miR-195a-5p) and decreases of 2 micrornas (miR-122-5p and miR-7a-1-5p) during hibernation. rna sequencing and in silico target prediction regarding 3 upregulated micrornas (miR-221-3p, miR-222-3p and miR-455-3p) found 13 target mrnas with significantly decreased expression during hibernation. The transfection of microrna mimics into cells showed that miR-222 and miR-455 reduced solute carrier family 16 member 4 (SLC16A4) and fatty acid synthase (FASN) mrna expression, respectively. Our results suggest that the increased levels of hepatic mirna during hibernation (miR-222-3p and miR-455-3p) negatively regulate the expression of targeted genes predicted to be involved in the transport of energy source and de novo fatty acid synthesis, is consistent with a regulatory role of these mirnas in energy metabolism in hibernating black bears.

关键词： Hibernation Liver Metabolism microrna non-coding rna Ursus

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Microrna dysregulation and its impact on apoptosis-related signaling pathways in myelodysplastic syndrome

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PATHOLOGY RESEARCH AND PRACTICE 2024年 261卷 155478页

作者： Hedayati, Neda Naeini, Mobina Safaei Sahebfosoul, Mohammad Mahdi Ale Mafi, Alireza Milasi, Yaser Eshaghi Rizaneh, Anahita Nabavi, Noushin Farahani, Najma Alimohammadi, Mina Ghezelbash, Behrooz Iran Univ Med Sci Sch Med Tehran Iran Isfahan Univ Med Sci Fac Med Dept Immunol Esfahan Iran Isfahan Univ Med Sci Dept Clin Biochem Sch Pharm & Pharmaceut Sci Esfahan Iran Isfahan Univ Med Sci Nutr & Food Secur Res Ctr Esfahan Iran Isfahan Univ Med Sci Dept Genet & Mol Biol Esfahan Iran Shahid Beheshti Univ Med Sci Sch Med Dept Immunol Tehran Iran

Myelodysplastic syndrome (MDS) holds a unique position among blood cancers, encompassing a spectrum of blood-related disorders marked by impaired maturation of blood cell precursors, bone marrow abnormalities, genetic instability, and a higher likelihood of progressing to acute myeloid leukemia. Micrornas (mirnas), short non-coding rna molecules typically 18-24 nucleotides in length, are known to regulate gene expression and contribute to various biological processes, including cellular differentiation and programmed cell death. Additionally, mirnas are involved in many aspects of cancer development, influencing cell growth, transformation, and apoptosis. In this study, we explore the impact of micrornas on cellular apoptosis in MDS.

关键词： Apoptosis Myelodysplastic syndrome Microrna non-coding rna

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