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Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence

BMC CANCER 2013年第1期13卷 1-11页

作者： Alaiyan, Bilal Ilyayev, Nadia Stojadinovic, Alexander Izadjoo, Mina Roistacher, Marina Pavlov, Vera Tzivin, Victoria Halle, David Pan, Honguang Trink, Barry Gure, Ali O. Nissan, Aviram Hadassah Hebrew Univ Med Ctr Surg Oncol Lab Dept Surg IL-91120 Jerusalem Israel Henry M Jackson Fdn Adv Mil Med Diagnost & Translat Res Ctr Gaithersburg MD 20879 USA Walter Reed Natl Med Ctr Dept Surg Div Surg Oncol Bethesda MD USA Johns Hopkins Sch Med Baltimore MD USA Bilkent Univ Dept Mol Biol & Genet Ankara Turkey Hadassah Hebrew Univ Med Ctr Ein Kerem Dept Surg Jerusalem Israel

Background: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding rna over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma- carcinoma sequence of CC tumorigenesis. Methods: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. rna was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Results: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 +/- 157.0;p = 0.0012);primary tumor tissue (RQ = 64.9 +/- 56.9;p = 0.0048);normal mucosa adjacent to primary tumor (RQ = 17.7 +/- 21.5;p = 0.09);lymph node, liver and peritoneal metastases (RQ = 11,414.5 +/- 12,672.9;119.2 +/- 138.9;816.3 +/- 2,736.1;p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. Conclusion: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process.

关键词： Colon cancer non-coding rna Biomarkers Adenoma Carcinoma

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Circrna_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway

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MOLECULAR BIOLOGY REPORTS 2024年第1期51卷 1067页

作者： Jin, Yichao He, Yongjing Wu, Yifei Wang, Xiaochuan Lyu, Lechun Zhang, Ke Ao, Chunping Xu, Liangheng First Peoples Hosp Yunnan Prov Dept Dermatol Kunming Yunnan Peoples R China Kunming Univ Sci & Technol Affiliated Hosp Dept Dermatol Kunming Yunnan Peoples R China Kunming Med Univ Affiliated Hosp 2 Dept Plast Surg Kunming Yunnan Peoples R China Kunming Med Univ Technol Transfer Ctr Kunming Yunnan Peoples R China First Peoples Hosp Yunnan Prov Dept Urinary Surg Kunming Yunnan Peoples R China Kunming Univ Sci & Technol Dept Ultrasound Affiliated Hosp Kunming Yunnan Peoples R China

BackgroundHypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circrna microarray analysis identified reduced expression of circrna_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circrna_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in ***-qPCR and FISH assays were used to assess the differential expression and localization of circrna_SLC8A1 in normal and HS tissues. Following modulation of circrna_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circrna_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circrna_SLC8A1 and downstream ***_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circrna_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. Circrna_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to mirna-27a-3p. mirna-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of mirna-27a-3p counteracted the effects of circrna_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway ***_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with mirna-27a-3p, thereby activating the Nrf2-ARE pathway. The circrna_SLC8A1/mirna-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy.

关键词： Hypertrophic scar Epithelial-mesenchymal transition Collagen deposition non-coding rna Nrf2-ARE pathway

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Evaluation of non-coding variation in GLUT1 deficiency

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DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY 2016年第12期58卷 1295-1302页

作者： Liu, Yu-Chi Lee, Jia Wei Audrey Bellows, Susannah T. Damiano, John A. Mullen, Saul A. Berkovic, Samuel F. Bahlo, Melanie Scheffer, Ingrid E. Hildebrand, Michael S. Univ Melbourne Dept Med Epilepsy Res Ctr Heidelberg Vic Australia Walter & Eliza Hall Inst Med Res Populat Hlth & Immun Div Parkville Vic Australia Florey Inst Heidelberg Vic Australia Univ Melbourne Royal Childrens Hosp Dept Paediat Parkville Vic Australia

AimLoss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations. We hypothesized that GLUT1 deficiency could be due to non-coding SLC2A1 variants. MethodWe performed whole exome sequencing of one proband with a GLUT1 phenotype and hypoglycorrhachia negative for SLC2A1 sequencing and copy number variants. We studied a further 55 patients with different epilepsies and low CSF glucose who did not have exonic mutations or copy number variants. We sequenced non-coding promoter and intronic regions. We performed mrna studies for the recurrent intronic variant. ResultsThe proband had a de novo splice site mutation five base pairs from the intron-exon boundary. Three of 55 patients had deep intronic SLC2A1 variants, including a recurrent variant in two. The recurrent variant produced less SLC2A1 mrna transcript. InterpretationFasting CSF glucose levels show an age-dependent correlation, which makes the definition of hypoglycorrhachia challenging. Low CSF glucose levels may be associated with pathogenic SLC2A1 mutations including deep intronic SLC2A1 variants. Extending genetic screening to non-coding regions will enable diagnosis of more patients with GLUT1 deficiency, allowing implementation of the ketogenic diet to improve outcomes.

关键词： GLUCOSE transporter 1 deficiency syndrome BLOOD-brain barrier disorders DNA copy number variations MUTATION (Biology) CEREBROSPINAL fluid non-coding rna TREATMENT

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Evaluation and Identification of Reliable Reference Genes for Pharmacogenomics, Toxicogenomics, and Small rna Expression Analysis

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JOUrnaL OF CELLULAR PHYSIOLOGY 2011年第10期226卷 2469-2477页

作者： Chen, Dongliang Pan, Xiaoping Xiao, Peng Farwell, Mary A. Zhang, Baohong E Carolina Univ Dept Biol Greenville NC 27858 USA E Carolina Univ Dept Math Greenville NC 27858 USA

Pharmacogenomics, toxicogenomics, and small rna expression analysis are three of the most active research topics in the biological, biomedical, pharmaceutical, and toxicological fields. All of these studies are based on gene expression analysis, which requires reference genes to reduce the variations derived from different amounts of starting materials and different efficiencies of rna extraction and cDNA synthesis. Thus, accurate normalization to one or several constitutively expressed reference genes is a prerequisite to valid gene expression studies. Although selection of reliable reference genes has been conducted in previous studies in several animals and plants, no research has been focused on pharmacological targets, and very few studies have had a toxicological context. More interestingly, no studies have been performed to identify reference genes for small rna analysis although small rna, particularly microrna (mirna)related research is currently one of the fastest-moving topics. In this study, using MCF-7 breast cancer cells as a model, we employed quantitative real-time PCR (qRT-PCR), one of the most reliable methods for gene expression analysis in many research fields, to evaluate and to determine the most reliable reference genes for pharmacogenomics and toxicogenomics studies as well as for small rna expression analysis. We tested the transcriptional expression of five protein-coding genes as well as five non-coding genes in MCF-7 cells treated with five different pharmaceuticals or toxicants [paclitaxel (PTX), gossypol (GOS), methyl jasmonate (JAS), L-nicotine (NIC), and melamine (mela)] and analyzed the stability of the selected reference genes by four different methods: geNorm, NormFinder, BestKeeper, and the comparative DCt method. According to our analysis, a protein-coding gene, hTBCA and four non-coding genes, hRNU44, hRNU48, hU6, and hRNU47, appear to be the most reliable reference genes for the five chemical treatments. Similar results were al

关键词： GENE expression PHARMACOGENOMICS TOXICOGENOMICS non-coding rna DNA synthesis PACLITAXEL POLYMERASE chain reaction GENETIC code

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Transcriptome structure variability in Saccharomyces cerevisiae strains determined with a newly developed assembly software

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BMC GENOMICS 2014年第1期15卷 1-15页

作者： Sardu, Alessandro Treu, Laura Campanaro, Stefano Univ Fribourg Div Biochem Dept Biol CH-1700 Fribourg Switzerland Tech Univ Denmark Dept Environm Engn DK-2800 Lyngby Denmark Univ Padua Dept Biol I-35131 Padua Italy

Background: rna-seq studies have an important role for both large-scale analysis of gene expression and for transcriptome reconstruction. However, the lack of software specifically developed for the analysis of the transcriptome structure in lower eukaryotes, has so far limited the comparative studies among different species and strains. Results: In order to fill this gap, an innovative software called ORA (Overlapped Reads Assembler) was developed. This software allows a simple and reliable analysis of the transcriptome structure in organisms with a low number of introns. It can also determine the size and the position of the untranslated regions (UTR) and of polycistronic transcripts. As a case study, we analyzed the transcriptional landscape of six S. cerevisiae strains in two different key steps of the fermentation process. This comparative analysis revealed differences in the UTR regions of transcripts. By extending the transcriptome analysis to yeast species belonging to the Saccharomyces genus, it was possible to examine the conservation level of unknown non-coding rnas and their putative functional role. Conclusions: By comparing the results obtained using ORA with previous studies and with the transcriptome structure determined with other software, it was proven that ORA has a remarkable reliability. The results obtained from the training set made it possible to detect the presence of transcripts with variable UTRs between S. cerevisiae strains. Finally, we propose a regulatory role for some non-coding transcripts conserved within the Saccharomyces genus and localized in the antisense strand to genes involved in meiosis and cell wall biosynthesis.

关键词： Saccharomyces cerevisiae Saccharomyces sensu-stricto Transcriptome assembly software Transcriptome variability UTR non-coding rna Cell wall Reproductive process in single-celled organism

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Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma

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CANCER GENE THERAPY 2015年第11期22卷 530-535页

作者： Najafi, Z. Sharifi, M. Javadi, G. Islamic Azad Univ Sci & Res Branch Dept Biol Tehran 14515775 Iran Isfahan Univ Med Sci Sch Med Dept Genet & Mol Biol Esfahan Iran

Micrornas (mirnas) are small non-coding rnas, 18-25 nucleotides long and have an important role in post-transcriptional regulation Of gene. Several aspects of cellular activities such as cell growth, proliferation and differentiation are regulated by mirnas. In Many cancers and malignancies, up- or downregulation of different mirnas has been reported. In human hepatocellular carcinoma (HCC), upregulation of miR-21 has been reported in human in vitro studies. Here, we made an assessment of the effect of miR-21 degradation on viability and apoptosis of HCC cell line (HepG2) using locked nucleic acid (LNA). At different time points (24, 48, 72 h) after LNA-anti-miR-21 transfection, 3-[4,5-dimethylthiaol-2-yl]-2, 5-diphenyl tetrazolium bromide assay and Annexin/propidium iodide staining were performed. The results show that miR-21 degradation can decrease the viability of cells, Mainly by induction of apoptosis and necrosis. These findings suggest that degradation Of miR-21 could be used as a novel approach in treatment of HCC.

关键词： Microrna Apoptosis Cell proliferation Liver -- Cancer non-coding rna Genetic regulation

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Small regulatory rnas of oral streptococci and periodontal bacteria

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JAPANESE DENTAL SCIENCE REVIEW 2021年 57卷 209-216页

作者： Oogai, Yuichi Nakata, Masanobu Kagoshima Univ Dept Oral Microbiol Grad Sch Med & Dent Sci Kagoshima 8908544 Japan

Small regulatory rnas (srnas) belong to a family of non-coding rnas, and many of which regulate expression of genes via interaction with mrna. The recent popularity of high-throughput next generation sequencers have presented abundant srna-related data, including srnas of several different oral bacterial species. Some srna candidates have been validated in terms of their expression and interaction with target mrnas. Since the oral cavity is an environment constantly exposed to various stimuli, such as fluctuations in temperature and pH, and osmotic pressure, as well as changes in nutrient availability, oral bacteria require rapid control of gene expression for adaptation to such diverse conditions, while regulation via interactions of srnas with mrna provides advantages for rapid adaptation. This review summarizes methods effective for identification and validation of srnas, as well as srnas identified to be associated with oral bacterial species, including cariogenic and periodontal pathogens, together with their confirmed and putative target genes. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of The Japanese Association for Dental Science. This is an open access article under the CC BY-NC-ND license (http://***/ licenses/by-nc-nd/4.0/).

关键词： Small regulatory rna non-coding rna Antisense rna Oral bacteria Streptococcus Periodontal pathogens

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The role of T cells in acute ischemic stroke

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BRAIN RESEARCH BULLETIN 2023年 196卷 20-33页

作者： Wang, Yi-Ran Cui, Wen-Qiang Wu, Hong-Yun Xu, Xiang-Dong Xu, Xiang-Qing Shandong Univ Tradit Chinese Med Coll Chinese Med Jinan Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Dept Neurol Jinan Peoples R China Shandong Univ Tradit Chinese Med Coll Clin Med 1 Jinan Peoples R China Shandong Univ Tradit Chinese Med Affiliated Hosp Expt Ctr Jinan Peoples R China

Acute ischemic stroke (AIS) is associated with high rates of disability and mortality, exerting a substantial impact on overall survival and health-related quality of life. Treatment of AIS remains challenging given that the underlying pathologic mechanisms remain unclear. However, recent research has demonstrated that the immune system plays a key role in the development of AIS. Numerous studies have reported infiltration of T cells into ischemic brain tissue. While some types of T cells can promote the development of inflammatory responses and aggravate ischemic damage in patients with AIS, other T cells appear to exert neuroprotective effects via immunosuppression and other mechanisms. In this review, we discuss the recent findings regarding the infiltration of T cells into ischemic brain tissue, and the mechanisms governing how T cells can facilitate tissue injury or neuroprotection in AIS. Factors influencing the function of T cells, such as intestinal microflora and sex differences, are also discussed. We also explore the recent research on the effect of non-coding rna on T cells after stroke, as well as the potential for specifically targeting T cells in the treatment of stroke patients.

关键词： Acute ischemic stroke T cell Immune response Neuroprotective effect Gut microbiome non-coding rna

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Enhancer Function: Mechanistic and Genome-Wide Insights Come Together

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MOLECULAR CELL 2014年第1期55卷 5-14页

作者： Plank, Jennifer L. Dean, Ann NIDDK Cellular & Dev Biol Lab NIH Bethesda MD 20892 USA

Enhancers establish spatial or temporal patterns of gene expression that are critical for development, yet our understanding of how these DNA cis-regulatory elements function from a distance to increase transcription of their target genes and shape the cellular transcriptome has been gleaned primarily from studies of individual genes or gene families. High-throughput sequencing studies place enhancer-gene interactions within the 3D context of chromosome folding, inviting a new look at enhancer function and stimulating provocative new questions. Here, we integrate these whole-genome studies with recent mechanistic studies to illuminate how enhancers physically interact with target genes, how enhancer activity is regulated during development, and the role of noncoding rnas transcribed from enhancers in their function.

关键词： GENE expression SPATIOTEMPORAL processes GENETIC transcription NUCLEOTIDE sequence GENE targeting non-coding rna

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Epigenetic dysregulation in glioma

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CANCER SCIENCE 2014年第4期105卷 363-369页

作者： Kondo, Yutaka Katsushima, Keisuke Ohka, Fumiharu Natsume, Atsushi Shinjo, Keiko Aichi Canc Ctr Div Epigen Res Inst Nagoya Aichi 4648681 Japan Aichi Canc Ctr Div Mol Oncol Res Inst Nagoya Aichi 4648681 Japan Nagoya Univ Sch Med Dept Neurosurg Nagoya Aichi 466 Japan Aichi Canc Ctr Div Mol Pathol Res Inst Nagoya Aichi 4648681 Japan

Given that treatment options for patients with glioblastoma are limited, much effort has been made to clarify the underlying mechanisms of gliomagenesis. Recent genome-wide genomic and epigenomic analyses have revealed that mutations in epigenetic modifiers occur frequently in gliomas and that dysregulation of epigenetic mechanisms is closely associated with glioma formation. Given that epigenetic changes are reversible, understanding the epigenetic abnormalities that arise in gliomagenesis might be key to developing more effective treatment strategies for glioma. In this review, we focus on the recent advancements in epigenetic research with respect to gliomas, consider how epigenetic mechanisms dynamically regulate tumor cells, including the cancer stem cell population, and discuss perspectives and challenges for glioma treatment in the near future.

关键词： Glioma stem cell DNA methylation epigenetics histone modification non-coding rna

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