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ncrnas-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

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MOLECULAR THERAPY NUCLEIC ACIDS 2021年 24卷 845-855页

作者： Lou, Weiyang Wang, Wenlong Chen, Jing Wang, Shuqian Huang, Yuan Zhejiang Univ Affiliated Hosp 1 Dept Breast Surg Coll Med Hangzhou 310003 Zhejiang Peoples R China Hangzhou Hosp Tradit Chinese Med Intens Care Unit Hangzhou Peoples R China Jiaxing Univ Dept Oncol Affiliated Hosp 1 Jiaxing 314000 Zhejiang Peoples R China Chinese Acad Sci Inst Basic Med & Canc IBMC Dept Breast Med Oncol Canc HospUniv Chinese Acad SciZhejiang Canc Hos Hangzhou 310022 Zhejiang Peoples R China

Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that semaphorin 3F (SEMA3F) plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of SEMA3F in HCC remains not fully determined. In this study, we first performed pan-cancer analysis for SEMA3F's expression and prognosis using The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that SEMA3F might be a potential oncogene in HCC. Subsequently, noncoding rnas (ncrnas) contributing to SEMA3F overexpression were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the TMPO-AS1/SNHG16-let-7c-5p axis was identified as the most potential upstream ncrna-related pathway of SEMA3F in HCC. Moreover, SEMA3F level was significantly positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncrnas-mediated upregulation of SEMA3F correlated with poor prognosis and tumor immune infiltration in HCC.

关键词： SEMA3F TMPO-AS1 SNHG16 let-7c-5p hepatocellular carcinoma tumor immune infiltration prognosis noncoding rna

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Peripheral blood micrornas and the COVID-19 patient: methodological considerations, technical challenges and practice points

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rna BIOLOGY 2021年第5期18卷 688-695页

作者： Pinilla, Lucia Benitez, Ivan D. Gonzalez, Jessica Torres, Gerard Barbe, Ferran de Gonzalo-Calvo, David Univ Hosp Arnau Vilanova & Santa Maria IRBLleida Translat Res Resp Med Avda Alcalde Rovira Roure 80 Lleida 25198 Spain Inst Hlth Carlos III CIBER Resp Dis CIBERES Madrid Spain Univ Lleida Univ Hosp Arnau Vilanova Santa Maria Resp Dept Translat Res Resp MedIRBLleida Lleida Spain

The COVID-19 emergency pandemic resulting from infection with SARS-CoV-2 represents a major threat to public health worldwide. There is an urgent clinical demand for easily accessible tools to address weaknesses and gaps in the management of COVID-19 patients. In this context, transcriptomic profiling of liquid biopsies, especially micrornas (mirnas), has recently emerged as a robust source of potential clinical indicators for medical decision-making. Nevertheless, the analysis of the circulating mirna signature and its translation to clinical practice requires strict control of a wide array of methodological details. In this review, we indicate the main methodological aspects that should be addressed when evaluating the circulating mirna profiles in COVID-19 patients, from preanalytical and analytical variables to the experimental design, impact of confounding, analysis of the data and interpretation of the findings, among others. Additionally, we provide practice points to ensure the rigour and reproducibility of mirna-based biomarker investigations of this condition.

关键词： Blood biomarker COVID-19 liquid biopsy methods microrna noncoding rna RT-qPCR SARS-CoV-2

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Deep sequencing reveals abundant noncanonical retroviral micrornas in B-cell leukemia/lymphoma

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2013年第6期110卷 2306-2311页

作者： Rosewick, Nicolas Momont, Melanie Durkin, Keith Takeda, Haruko Caiment, Florian Cleuter, Yvette Vernin, Celine Mortreux, Franck Wattel, Eric Burny, Arsene Georges, Michel Van den Broeke, Anne Univ Liege Unit Anim Genom Grp Interdisciplinaire Genoprote Appl B-4000 Liege Belgium Univ Libre Bruxelles Lab Expt Hematol Inst Jules Bordet B-1000 Brussels Belgium Ecole Normale Super Lyon Unite Mixte Rech 5239 F-69008 Lyon France

Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy, however, remains poorly understood, especially as viral mrna/protein are tightly silenced in tumors. Here, using deep sequencing of broad windows of small rna sizes in the bovine leukemia virus ovine model of leukemia/lymphoma, we provide in vivo evidence of the production of noncanonical rna polymerase III (Pol III)-transcribed viral micrornas in leukemic B cells in the complete absence of Pol II 5'-LTR-driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, bovine leukemia virus micrornas represent similar to 40% of all micrornas in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and/or viral targets. Bovine leukemia virus micrornas are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent micrornas subvert cellular and viral pathways will contribute to deciphering the intricate perturbations that underlie malignant transformation.

关键词： noncoding rna oncogenesis retrovirus silencing HTLV-1

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The SLC19A1-AS/miR-1343/WNT11 axis is a novel positive regulatory cerna network governing goat granulosa cell proliferation

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INTErnaTIONAL JOUrnaL OF BIOLOGICAL MACROMOLECULES 2024年第Pt 2期264卷 130658页

作者： Zhang, Runan Zhou, Zuyang Wang, Peng He, Xiaoyun Liu, Yufang Chu, Mingxing Chinese Acad Agr Sci CAAS Inst Anim Sci State Key Lab Anim Biotech Breeding Beijing 100193 Peoples R China

Long noncoding rnas (lncrnas), as competitive endogenous rnas (cernas), can directly or indirectly affect the proliferation and apoptosis of granulosa cells by regulating microrna (mirna) pathways. A cerna network of the SLC19A1-AS-miR-1343-WNT11 axis was constructed via comprehensive transcriptome sequencing of ovaries from goats with various fertility levels to further elucidate the function and regulatory mechanism of SLC19A1AS in modulating miR-1343 and WNT11 during granulosa cell proliferation and apoptosis. Subsequent validation experiments were conducted in vitro using granulosa cells. In these experiments, we performed rna immunoprecipitation (RIP) and identified SLC19A1-AS as a cerna in goat granulosa cells that promoted proliferation. Through bioinformatics prediction, luciferase reporter gene assays, and rna pulldown assays, we confirmed that SLC19A1-AS acts as a sponge for miR-1343, preventing its binding to WNT11 mrna and thereby increasing the expression of WNT11. This interaction also influenced the proliferation and apoptosis of granulosa cells. Our study systematically validated the biological function of the lncrna-mirna-mrna cerna network in goat ovaries and revealed the potential regulatory mechanism by which SLC19A1-AS functions as a cerna in granulosa cells. These findings are expected to provide an important experimental foundation for further elucidating the physiological regulatory network of the ovary and contributing to reproductive health in goats.

关键词： Granulosa cell proliferation noncoding rna Goat

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Analysis of multi-omics data on the relationship between epigenetic changes and nervous system disorders caused by exposure to environmentally harmful substances

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ENVIRONMENTAL TOXICOLOGY 2022年第4期37卷 802-813页

作者： Yu, So Yeon Koh, Eun Jung Kim, Seung Hwan Song, Byeongwook Lee, Ji Su Son, Sang Wook Seo, Hyemyung Hwang, Seung Yong Hanyang Univ Dept Mol & Life Sci 55 Hanyangdaehak Ro Ansan Gyeonggi Do South Korea Hanyang Univ Dept Bionano Engn Ansan South Korea Hanyang Univ Dept Mol & Life Sci Ctr Bionano Intelligence Educ & Res Ansan South Korea Korea Univ Dept Dermatol Coll Med Seoul South Korea Hanyang Univ Dept Appl Artificial Intelligence Ansan South Korea

Environmentally hazardous substances and exposure to these can cause various diseases. Volatile organic compounds can easily evaporate into the atmosphere, thereby exerting toxic effects through either the skin or respiratory tract exposures. Toluene, a neurotoxin, has been widely used in various industries. However, it has a detrimental effect on the nervous system (such as hallucinations or memory impairment), while data on the mechanism underlaying its harmful effects remain limited. Therefore, this study investigates the effect of toluene on the nervous system via epigenetic and genetic changes of toluene-exposed individuals. We identified significant epigenetic changes and confirmed that the affected abnormally expressed genes negatively influenced the nervous system. In particular, we confirmed that the miR-15 family, upregulated by toluene, downregulated ABL2, which could affect the R as signaling pathway resulting in neuronal structural abnormalities. Our study suggests that miR-15a-5p, miR-15b-5p, miR-16-5p, miR-301a-3p, and lncrna NEAT1 may represent effective epigenomic markers associated with neurodegenerative diseases caused by toluene.

关键词： epigenetic neurodegenerative diseases noncoding rna Ras signaling toluene

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Markers associated with neuron-specific Ube3a imprinting during neuronal differentiation of mouse embryonic stem cells

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CYTOTECHNOLOGY 2018年第1期70卷 45-53页

作者： Eitoku, Masamitsu Kato, Hidemasa Suganuma, Narufumi Kiyosawa, Hidenori Kochi Univ Kochi Med Sch Dept Environm Med Oko Cho Kohasu Nanko Ku Kochi 7838505 Japan Ehime Univ Grad Sch Med Div Funct Histol Dept Funct Biomed Toon Ehime 7910295 Japan Chiba Inst Technol Dept Life Sci Narashino Chiba 2750016 Japan

Understanding gene expression in the brain requires allele-specific transcriptome analysis because of the presence of neuron-specific imprinted genes, which are expressed in a neuron-specific and parent-of-origin-specific manner. Ube3a is a neuron-specific imprinted gene with an expression pattern that changes from biallelic to maternal only (Ube3a imprinting) during differentiation. Because Ube3a imprinting occurs only in neurons, it has the potential to be a marker to assess the quality of neurons produced by in vitro neuronal differentiation of embryonic stem cells (ESCs). For the analysis of Ube3a imprinting, genetic polymorphisms between the two alleles are necessary to identify the parental origin of each. However, ESCs derived from commonly used inbred mouse strains have no genetic polymorphisms. To overcome this problem, we examined 10 markers of neurogenesis to determine whether they were associated with Ube3a imprinting. We measured the relative expression levels of these 10 gene markers and assessed the Ube3a imprinting status of 54 neuron samples differentiated under various in vitro conditions. Then we divided the samples into two groups depending on their Ube3a imprinting status and selected markers statistically associated with Ube3a imprinting. The identified markers included the antisense noncoding transcript of Ube3a and a mature neuron marker Mtap2, consistent with the markers we used empirically in our previous study to assess the quality of differentiated neurons. These findings provide new quality control criteria for differentiated neurons, and could also be applied to human ESCs and induced pluripotent stem cells.

关键词： Ube3a imprinting Embryonic stem cell In vitro neuronal differentiation Mus musculus molossinus Mtap2 noncoding rna SNP ratio quantification

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Regulatory and therapeutic implications of competing endogenous rna network in breast cancer progression and metastasis: A review

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INTErnaTIONAL JOUrnaL OF BIOLOGICAL MACROMOLECULES 2024年第Part2期266卷 131075页

作者： Saranya, I. Dharshini, V. Sowfika Akshaya, R. L. Subhashini, P. Sakthi Selvamurugan, N. SRM Inst Sci & Technol Fac Engn & Technol Sch Bioengn Dept Biotechnol Kattankulathur 603203 Tamil Nadu India

Breast cancer (BC) is a global health concern, and development of diagnostic tools and targeted treatments for BC remains challenging. Therapeutic approaches for BC often involve a combination of surgery, radiation therapy, chemotherapy, targeted therapy, and hormone therapy. In recent years, there has been a growing interest in the role of noncoding rnas (ncrnas), including long ncrnas (lncrnas) and micrornas (mirnas), in BC and their therapeutic implications. Various biological processes such as cell proliferation, migration, and apoptosis rely on the activities of these ncrnas, and their dysregulation has been implicated in BC progression. The regulatory function of the competitive endogenous rna (cerna) network, which comprises lncrnas, mirnas, and mrnas, has been the subject of extensive pathophysiological research. Most lncrnas serve as molecular sponges for mirnas and sequester their activities, thereby regulating the expression of target mrnas and contributing to the promotion or inhibition of BC progression. This review summarizes recent findings on the role of cerna networks in BC progression, metastasis, and therapeutic resistance, and highlights the association of cerna networks with transcription factors and signaling pathways. Understanding the cerna network can lead to the discovery of biomarkers and targeted treatment methods to prevent the spread and metastasis of BC.

关键词： Breast cancer Metastasis noncoding rna

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Microrna-339-5p Down-regulates Protein Expression of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 (BACE1) in Human Primary Brain Cultures and Is Reduced in Brain Tissue Specimens of Alzheimer Disease Subjects*

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2014年第8期289卷 5184-5198页

作者： Long, Justin M. Ray, Balmiki Lahiri, Debomoy K. Indiana Univ Sch Med Mol Neurogenet Lab Inst Psychiat Res Dept Psychiat Indianapolis IN 46202 USA Indiana Univ Sch Med Dept Med & Mol Genet Indianapolis IN 46202 USA

Background: BACE1 is the rate-limiting enzyme in the synthesis of A from amyloid precursor protein. Results: Human miR-339-5p negatively regulates BACE1 and A in human brain cultures and is reduced in AD specimens. Conclusion: Human miR-339-5p physiologically regulates human BACE1 protein expression and A and is dysregulated in the AD brain. Significance: miR-339-5p represents a novel drug target in AD. Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid- (A) peptide as neuritic plaques in the brain. The short A peptide is derived from the large transmembrane A precursor protein (APP). The rate-limiting step in the production of A from APP is mediated by the -site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to excess A deposition is implicated in sporadic AD. Thus, elucidating the full complement of regulatory pathways that control BACE1 expression is key to identifying novel drug targets central to the A-generating process. Micrornas (mirnas) are expected to participate in this molecular network. Here, we identified a known mirna, miR-339-5p, as a key contributor to this regulatory network. Two distinct miR-339-5p target sites were predicted in the BACE1 3-UTR by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3-UTR reporter construct resulted in significant reduction in reporter expression. Mutation of both target sites eliminated this effect. Delivery of the miR-339-5p mimic also significantly inhibited expression of BACE1 protein in human glioblastoma cells and human primary brain cultures. Delivery of target protectors designed against the miR-339-5p BACE1 3-UTR target sites in primary human brain cultures significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to be significantly reduced in brain specimens isolated from AD patients as compared with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in human brain cells and is most likely dysregul

关键词： Aging Alzheimer Disease Gene Regulation Microrna Secretases -Peptide Dementia Human Brain Tissue Human Neuron noncoding rna

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Genome-wide and Systematic Identification of noncoding rnas During Development

Genome-wide and Systematic Identification of Noncoding RNAs ...

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中国遗传学会“发育、遗传和疾病”研讨会

作者： Dahai Zhu National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,5 Dong Dan San Tiao,Beijing 100005,China.

Non-protein-coding rnas(ncrnas),which function at the rna level,consist of transcripts that do not have any clear“Open Reading Frame”(ORF)and are very difficult to predict from genomic sequences,ncrnas have been grouped in several classes of transcripts according to their number of nucleotides,sirnas(21-28nt),mirnas(19-25nt),pirnas(30-35nt),small rnas(70-500nt),large rnas(1000-10,000nt).As for functions of ncrnas,they are implicated in different molecular,cellular and organismal events in eukaryotic cells,including dosage compensation,genomic imprinting,gene expression regulation,and protein trafficking. Highlightly,the importance of small ncrnas that act as regulators of transcription,rna modification or stability,and mrna translation is becoming increasingly *** we report the genome-wide and systematic identification of small ncrnas(50-500nt)during *** constructed several ncrna libraries of human,mouse and chicken tissues,and found 123 new ncrnas,including 21 HACA-snorna,27 CD-snorna,and 75 unclassified *** ncrnas showed the tissue specific expression pattern by Northern *** functional analysis of these ncrnas could be important for our understanding of regulatory network of protein-coding gene expressions during development.

关键词： noncoding rna development human mouse chicken

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Identification of micrornas and Other Tiny noncoding rnas by cDNA Cloning

Identification of microRNAs and Other Tiny Noncoding RNAs by...

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作者： Victor Ambros Rosalind C. Lee

Micrornas (mirnas) and other small rnas can be identified by cloning and sequencing cDNAs prepared from the ∼22-nt fraction of total rna. Methods are described for the construction of cDNA libraries from small noncoding rnas through the use of T4 rna ligase, reverse transcriptase, and polymerase chain reaction. cDNAs are cloned in λ or plasmid vectors, and the sequences are compared to annotated genomic sequence databases, and analyzed by rna folding programs to distinguish mirna sequences from other small rnas of similar size. Northern blot hybridization is used to confirm the expression of small rnas in vivo. less

关键词： Northern Blot PCR Fractionation Total rna Extraction Gel Electrophoresis Shadowing (Histology) Reverse Transcription PCR Directional Cloning NCBI BLAST rna Secondary Structure Prediction Library Preparation Database Search Electroblotting cDNA sequencing DNA Ligation rna folding rna ligase microrna noncoding rna SMART cDNAs

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