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OBJECTIVE: Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. METHODS: We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. RESULTS: Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). CONCLUSION: Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.
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Adenocarcinoma , Neoplasias Gástricas , Neoplasias do Colo do Útero , Adenocarcinoma/genética , Adenocarcinoma/patologia , Citidina Desaminase/genética , Feminino , Humanos , Antígenos de Histocompatibilidade Menor/genética , Mutação , Recidiva Local de Neoplasia , Prognóstico , Neoplasias Gástricas/genética , Neoplasias do Colo do Útero/genéticaRESUMO
Traditional phylogenies inferred from chloroplast DNA fragments have not obtained a well-resolved evolutionary history for the backbone of Apioideae, the largest subfamily of Apiaceae. In this study, we applied the genome skimming approach of next-generation sequencing to address whether the lack of resolution at the tip of the Apioideae phylogenetic tree is due to limited information loci or the footprint of ancient radiation. A total of 90 complete chloroplast genomes (including 23 newly sequenced genomes and covering 20 major clades of Apioideae) were analyzed (RAxML and MrBayes) to provide a phylogenomic reconstruction of Apioideae. Dating analysis was also implemented using BEAST to estimate the origin and divergence time of the major clades. As a result, the early divergences of Apioideae have been clarified but the relationship among its distally branching clades (Group A) was only partially resolved, with short internal branches pointing to an ancient radiation scenario. Four major clades, Tordyliinae I, Pimpinelleae I, Apieae and Coriandreae, were hypothesized to have originated from chloroplast capture events induced by early hybridization according to the incongruence between chloroplast-based and nrDNA-based phylogenetic trees. Furthermore, the variable and nested distribution of junction positions of LSC (Large single copy region) and IRB (inverted repeat region B) in Group A may reflect incomplete lineage sorting within this group, which possibly contributed to the unclear phylogenetic relationships among these clades inferred from plastome data. Molecular clock analysis revealed the chloroplast capture events mainly occurred during the middle to late Miocene, providing a geological and climate context for the evolution of Apioideae.
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Apiaceae/genética , Evolução Molecular , Genoma de Cloroplastos/genética , Filogenia , Plastídeos/genética , Análise de Sequência de DNARESUMO
tRNA-derived small non-coding RNAs (tsncRNAs), a class of newly defined small non-coding RNA, have been considered to be involved in various cellular biological processes through regulating gene expression at both transcriptional and post-transcriptional level. However, the presence of circulating tsncRNAs and their diagnostic potential is largely unclear. In this study, we investigate the serum-derived public transcriptome data from ovarian tumor patients and non-cancer controls, and find that circulating tsncRNAs cover a high proportion of total small RNA and are non-random degradation products in serum (ranging from 2.5-29.4%), which are enriched in several specific types of related tRNA (e.g., Gly-tRNA). Particularly, four tsncRNAs are differentially expressed in serum from cancer patients compared to those from healthy controls, and can predict abnormal cell proliferation with high accuracy. Our results reveal the ubiquitous presence of circulating tsncRNAs in serum, and diagnostic potential of specific tsncRNAs for ovarian tumor.
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Biomarcadores Tumorais , Ácidos Nucleicos Livres , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Pequeno RNA não Traduzido , RNA de Transferência , Feminino , Humanos , Neoplasias Ovarianas/sangue , Prognóstico , Curva ROCRESUMO
Urophysa is a Chinese endemic genus comprising two species, Urophysa rockii and Urophysa henryi. In this study, we sequenced the complete chloroplast (cp) genomes of these two species and of their relative Semiquilegia adoxoides. Illumina sequencing technology was used to compare sequences, elucidate the intra- and interspecies variations, and infer the phylogeny relationship with other Ranunculaceae family species. A typical quadripartite structure was detected, with a genome size from 158,473 to 158,512 bp, consisting of a pair of inverted repeats separated by a small single-copy region and a large single-copy region. We analyzed the nucleotide diversity and repeated sequences components and conducted a positive selection analysis by the codon-based substitution on single-copy coding sequence (CDS). Seven regions were found to possess relatively high nucleotide diversity, and numerous variable repeats and simple sequence repeats (SSR) markers were detected. Six single-copy genes (atpA, rpl20, psaA, atpB, ndhI, and rbcL) resulted to have high posterior probabilities of codon sites in the positive selection analysis, which means that the six genes may be under a great selection pressure. The visualization results of the six genes showed that the amino acid properties across each column of all species are variable in different genera. All these regions with high nucleotide diversity, abundant repeats, and under positive selection will provide potential plastid markers for further taxonomic, phylogenetic, and population genetics studies in Urophysa and its relatives. Phylogenetic analyses based on the 79 single-copy genes, the whole complete genome sequences, and all CDS sequences showed same topologies with high support, and U. rockii was closely clustered with U. henryi within the Urophysa genus, with S. adoxoides as their closest relative. Therefore, the complete cp genomes in Urophysa species provide interesting insights and valuable information that can be used to identify related species and reconstruct their phylogeny.
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Cloroplastos/genética , Genes de Plantas , Genoma de Cloroplastos , Ranunculaceae/genética , Sequência de Aminoácidos , Evolução Biológica , China , Mapeamento Cromossômico , Códon , Variação Genética , Tamanho do Genoma , Sequências Repetidas Invertidas , Filogenia , Filogeografia , Folhas de Planta/genética , Ranunculaceae/classificação , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sequenciamento Completo do GenomaRESUMO
Lilium henrici Franchet, which belongs to the family Liliaceae, is an endangered plant native to China. The wild populations of L. henrici have been largely reduced by habitat degradation or loss. In our study, we determined the whole chloroplast genome sequence for L. henrici and compared its structure with other Lilium (including Nomocharis) species. The chloroplast genome of L. henrici is a circular structure and 152,784 bp in length. The large single copy and small single copy is 82,429 bp and 17,533 bp in size, respectively, and the inverted repeats are 26,411 bp in size. The L. henrici chloroplast genome contains 116 different genes, including 78 protein coding genes, 30 tRNA genes, 4 rRNA genes, and 4 pseudogenes. There were 51 SSRs detected in the L. henrici chloroplast genome sequence. Genic comparison among L. henrici with other Lilium (including Nomocharis) chloroplast genomes shows that the sequence lengths and gene contents show little variation, the only differences being in three pseudogenes. Phylogenetic analysis revealed that N. pardanthina was a sister species to L. henrici. Overall, this study, providing L. henrici genomic resources and the comparative analysis of Lilium chloroplast genomes, will be beneficial for the evolutionary study and phylogenetic reconstruction of the genus Lilium, molecular barcoding in population genetics.
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Genoma de Cloroplastos , Genômica , Lilium/genética , Códon , Biologia Computacional/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Lilium/classificação , Repetições de Microssatélites , Anotação de Sequência Molecular , FilogeniaRESUMO
Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies.
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Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.
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Variação Genética , Leucopenia/etiologia , Mercaptopurina/efeitos adversos , Variantes Farmacogenômicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirofosfatases/genética , Adolescente , Criança , Predisposição Genética para Doença , Genótipo , Humanos , Leucopenia/diagnóstico , Mercaptopurina/uso terapêutico , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
BACKGROUND: Selenium, a natural microelement with both nutritional and toxicological properties, is intertwined with tumorigenesis and progression. However, it is not fully understood how selenium metabolism affects immune response and cancer biology. METHODS: We estimated selenium metabolism by Gene Set Enrichment Analysis (GSEA) to delineate the selenium metabolism landscape using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and a integrated pan-cancer single-cell dataset. We systematically explored the prognostic implications of selenium metabolism and selenium-related regulatory patterns. The therapeutic value of selenium metabolism was explored through machine learning and examined in several immunotherapy cohorts. The heterogeneity and underlying mechanism of selenium metabolism were investigated by cellâcell communication analysis at the single-cell level. RESULTS: A GSEA analysis based on 86 genes was used to evaluate the selenium metabolism landscape. The selenium metabolism score exhibited prognostic value in predicting the lower risk of mortality, possibly due to its correlation with multiple cancer hallmarks, including a positive correlation with complement (R = 0.761, P < 0.001), inflammatory response (R = 0.663, P < 0.001), apoptosis (R = 0.626, P < 0.001), hypoxia (R = 0.587, P < 0.001), reactive oxygen species (ROS) (R = 0.558, P < 0.001), and interferon gamma response (R = 0.539, P < 0.001). We also observed heterogeneity in the relationship between selenium metabolism and immunity across different cancers. Based on selenium-related genes, we constructed a machine learning model with area under the ROC curve (AUC) of 0.82 in predicting immune checkpoint inhibitor (ICI)-based immunotherapy response. Single-cell selenium metabolism quantification revealed that adjacent and tumor tissues had higher selenium metabolism compared with normal tissues, especially in epithelial cells, fibroblasts and macrophages. The communication between high-selenium epithelium and high-selenium fibroblast was significantly higher than other cells, especially in cytokines, chemokines, collagen, Wnt, VEGF, IGF and FGF pathways. CONCLUSION: Our study provides a comprehensive landscape of selenium metabolism levels and diverse regulatory patterns in different cancers, deepening the understanding of selenium's roles in tumorigenesis and immunity.
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Neoplasias , Selênio , Humanos , Neoplasias/genética , Carcinogênese , Apoptose , Análise de Sequência de RNARESUMO
Introduction: Immature ovarian teratomas are a type of malignant germ cell tumor composed of complicated cell types and are characterized by pathological features of immature neuroectodermal tubules/rosettes. However, there is a lack of understanding of patient-derived immature ovarian teratomas (PDT) at the single cell level. Moreover, whether stem cell lines derived from immature teratomas (CDT) can be used as models for research on PDT remains to be elucidated. Methods: Single-cell RNA sequencing (scRNA-seq) and subsequent bioinformatic analysis was performed on three patient-derived immature ovarian teratomas (PDT) samples to reveal the heterogeneity, evolution trajectory, and cell communication within the tumor microenvironment of PDT. Validations were conducted in additional seven samples through multiplex immunofluorescence. Result: A total of qualified 22,153 cells were obtained and divided into 28 clusters, which can match to the scRNA-seq annotation of CDT as well as human fetal Cell Atlas, but with higher heterogeneity and more prolific cell-cell crosstalk. Radial glia cells (tagged by SOX2) and immature neuron (tagged by DCX) exhibited mutually exclusive expression and differentiated along distinct evolutionary trajectory from cycling neural progenitors. Proportions of these neuroectodermal cell subtypes may play important roles in PDT through contributing to the internal heterogeneity of PDTs. Moreover, the immune cells in PDTs were infiltrated rather than teratoma-derived, with more abundant macrophage in immature neuron than those in radial glia cells, and the infiltrated macrophage subtypes (i.e., M1 and M2) were significantly correlated to clinical grade. Overall, suppressed evolution process and transcriptome regulation in neuroectodermal cells, reduced cell-cell crosstalk, higher M1/M2 proportion ratio, and enhanced T cell effects in tumor microenvironment are enriched in patients with favorable prognosis. Discussion: This study provides a comprehensive profile of PDT at the single cell level, shedding light on the heterogeneity and evolution of neuroectodermal cells within PDTs and the role of immune cells within the tumor microenvironment. Also, our findings highlight the potential usage of CDTs as a model for research on PDT.
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Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Teratoma , Feminino , Humanos , Transcriptoma , Teratoma/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Microambiente Tumoral/genéticaRESUMO
Average nucleotide identity (ANI) is a prominent approach for rapidly classifying archaea and bacteria by recruiting both whole genomic sequences and draft assemblies. To evaluate the feasibility of ANI in virus taxon demarcation, 685 poxviruses were assessed. Prior to the analysis, the fragment length and threshold of the ANI value were optimized as 200 bp and 98 per cent, respectively. After ANI analysis and network visualization, the resulting sixty-one species (ANI species rank) were clustered and largely consistent with the groupings found in National Center for Biotechnology Information Virus [within the International Committee on Taxonomy of Viruses (ICTV) Master Species List]. The species identities of thirty-four other poxviruses (excluded by the ICTV Master Species List) were also identified. Subsequent phylogenetic analysis and Guanine-Cytosine (GC) content comparison done were found to support the ANI analysis. Finally, the BLAST identity of concatenated sequences from previously identified core genes showed 91.8 per cent congruence with ANI analysis at the species rank, thus showing potential as a marker gene for poxviruses classification. Collectively, our results reveal that the ANI analysis may serve as a novel and efficient method for poxviruses demarcation.
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Gastric cancer (GC) is one of the most common cancers and one of the leading causes of cancer-related death worldwide. Precise diagnosis and evaluation of GC, especially using noninvasive methods, are fundamental to optimal therapeutic decision-making. Despite the recent rapid advancements in technology, pretreatment diagnostic accuracy varies between modalities, and correlations between imaging and histological features are far from perfect. Artificial intelligence (AI) techniques, particularly hand-crafted radiomics and deep learning, have offered hope in addressing these issues. AI has been used widely in GC research, because of its ability to convert medical images into minable data and to detect invisible textures. In this article, we systematically reviewed the methodological processes (data acquisition, lesion segmentation, feature extraction, feature selection, and model construction) involved in AI. We also summarized the current clinical applications of AI in GC research, which include characterization, differential diagnosis, treatment response monitoring, and prognosis prediction. Challenges and opportunities in AI-based GC research are highlighted for consideration in future studies.
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PURPOSE: Long noncoding RNA (LncRNA) containing microRNA host gene is an interesting type of LncRNA. MicroRNA-31 (miR-31)-host gene LncRNA (MIR31HG) have been recognized as an oncogene in many cancers, but not in osteosarcoma (OS). Interestingly, MIR31HG/miR-31 could not regulate each other's expression in certain cancer, suggesting that the role of MIR31HG in cancer is independent of miR-31. We here investigated the function and potential mechanism of MIR31HG in OS. METHODS: OS tissues and adjacent non-tumor tissues (n=40) were collected to determine the expressions of MIR31HG by paired t-test. We here identified the miRNAs predicted to be bound to MIR31HG and investigated the impacts of MIR31HG on cell growth and metastasis of OS cells by CCK-8, flow cytometry, Transwell assay, Western blot, etc. in vitro and in vivo. RESULTS: MIR31HG was upregulated in OS tissues and OS cell lines. The patients with high expression of MIR31HG have high tumor stages and distant metastasis. Tumor suppressor miR-361, but not miR-31, was confirmed to be sponged directly by MIR31HG in OS cells and was down-regulated in OS cell lines. Knockdown of MIR31HG restored the expression of miR-361. Restoration of miR-361 level in Saos-2 and U2OS cells induced cell apoptosis and G1/S arrest, inhibited proliferation and migration, which was, however, abrogated by MIR31HG. Mechanistically, cell growth and metastasis-related target genes of MIR-361 including VEGF, FOXM1 and Twist were de-repressed in OS cells by MIR31HG overexpression, leading to upregulated BCL2, CCND1 and epithelial-mesenchymal transition (EMT) phenotype. Patients with high expression of MIR31HG also showed more VEGF, FOXM1 and Twist levels. Overexpression of MIR31HG in vivo also promoted tumor growth via inhibition of miR-361 signals and elevated the expression of VEGF, FOXM1 and Twist for tumor growth. CONCLUSION: MIR31HG acts as an oncogene in OS for tumor progression via regulation of tumor suppressor miR-361 and its target genes.
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The Qinghai-Tibet Plateau (QTP) has been biogeographically divided into the eastern monsoonal and the western continental climatic zones along the 500 mm isohyet. However, this biogeographic hypothesis has been rarely tested using a phylogeographic approach. The members of the genus Allium subgenus Cyathophora coincidentally distribute across this biogeographical divide. Intriguingly, Allium fasciculatum of subgenus Amerallium co-occurs in the distribution range of subgenus Cyathophora. To illuminate the role of this biogeographic divide on the genetic divergence, we genotyped 466 individuals of 52 populations of subgenus Cyathophora and 110 individuals of 19 populations of A. fasciculatum using three chloroplast DNA fragments, whole nrITS and nine nuclear microsatellite loci, supplemented with the present environmental space and paleo-distribution modeling. Our phylogeographical evidence recovered the concordant east-west genetic breaks both for subgenus Cyathophora and A. fasciculatum along the 500 mm isohyet. The divergence time estimations and environmental niche differentiations suggested this east-west genetic breaks could have been triggered by the climatic-induced vicariance during the early Pleistocene. Noticeably, this split within subgenus Cyathophora could have been deepened by the morphological vicariance from the eastern umbel to the western spicate, while that within A. fasciculatum could have been obscured due to the pollen flows from the east to west caused by the postglacial expansion. The genetic structures and ecological niche modelings (ENMs) recovered the distinct responses to the Quaternary climatic oscillations for species constricted to different climatic zones, further highlighting the profound effect of the climatic differences and tectonic uplifts on the genetic diversification. Overall, our findings offer strong evidence for the existence of a biogeographic divide between the eastern monsoonal and the west continental climatic zones of the QTP nearly along the 500 mm isohyet.
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The genus Allium (Amaryllidaceae, Allioideae) is one of the largest monocotyledonous genera and it includes many economically important crops that are cultivated for consumption or medicinal uses. Recent advances in molecular phylogenetics have revolutionized our understanding of Allium taxonomy and evolution. However, the phylogenetic relationships in some Allium sections (such as the Allium section Daghestanica) and the genetic bases of adaptative evolution, remain poorly understood. Here, we newly assembled six chloroplast genomes from Chinese endemic species in Allium section Daghestanica and by combining these genomes with another 35 allied species, we performed a series of analyses including genome structure, GC content, species pairwise Ka/Ks ratios, and the SSR component, nucleotide diversity and codon usage. Positively selected genes (PSGs) were detected in the Allium lineage using the branch-site model. Comparison analysis of Bayesian and ML phylogeny on CCG (complete chloroplast genome), SCG (single copy genes) and CDS (coding DNA sequences) produced a well-resolved phylogeny of Allioideae plastid lineages, which illustrated several novel relationships with the section Daghestanica. In addition, six species in section Daghestanica showed highly conserved structures. The GC content and the GC3s content in Allioideae species exhibited lower values than studied non-Allioideae species, along with elevated pairwise Ka/Ks ratios. The rps2 gene was lost in all examined Allioideae species, and 10 genes with significant posterior probabilities for codon sites were identified in the positive selection analysis, seven of them are associated with photosynthesis. Our study uncovered a new species relationship in section Daghestanica and suggested that the selective pressure has played an important role in Allium adaptation and evolution, these results will facilitate our further understanding of evolution and adaptation of species in the genus Allium.
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OBJECTIVES: Autophagy, a highly conserved lysosomal degradation process in eukaryotic cells, can digest long-lived proteins and damaged organelles through vesicular trafficking pathways. Nowadays, mechanisms of autophagy have been gradually elucidated and thus the discovery of small-molecule drugs targeting autophagy has always been drawing much attention. So far, some autophagy-related web servers have been available online to facilitate scientists to obtain the information relevant to autophagy conveniently, such as HADb, CTLPScanner, iLIR server and ncRDeathDB. However, to the best of our knowledge, there is not any web server available about the autophagy-modulating compounds. METHODS: According to published articles, all the compounds and their relations with autophagy were anatomized. Subsequently, an online Autophagic Compound Database (ACDB) (http://www.acdbliulab.com/) was constructed, which contained information of 357 compounds with 164 corresponding signalling pathways and potential targets in different diseases. RESULTS: We achieved a great deal of information of autophagy-modulating compounds, including compounds, targets/pathways and diseases. ACDB is a valuable resource for users to access to more than 300 curated small-molecule compounds correlated with autophagy. CONCLUSIONS: Autophagic compound database will facilitate to the discovery of more novel therapeutic drugs in the near future.
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Autofagia/efeitos dos fármacos , Bases de Dados de Compostos Químicos , Humanos , Transdução de Sinais , Bibliotecas de Moléculas PequenasRESUMO
The long noncoding RNA (LncRNA) SNHG7 (small nuclear RNA host gene 7) is a novel LncRNA and functions as an oncogene to promote tumor proliferation and inhibits apoptosis in many cancers. However, the role of SNHG7 in osteosarcoma (OS) remains to be further investigated. In this study, OS tissues and corresponding relative normal tissues (n = 30) were collected to determine the expression of SNHG7 in OS. The results indicated that high SNHG7 level in OS correlated with high Enneking stage, distant metastasis, and short overall survival time of OS patients. Moreover, miRNA-34a (miR-34a) is a classic tumor suppressor. Bioinformatic analysis predicted that SNHG7 harbored miR-34a binding sites, and the authors found that SNHG7 negatively correlated with miR-34a in OS tissues and the SNHG7 inhibition induced the restoration of miR-34a in OS cell lines MG63 and SaOS2, leading to the reactivation of miR-34a-mediated tumor suppression. Knockdown of SNHG7 in tumor cells significantly impaired the cell vitality, migration and invasion or TGF-ß-induced epithelial-mesenchymal transition (EMT), induced apoptosis, and G1/S arrest via miR-34a. Mechanistically, the targets of miR-34a could be upregulated by SNHG7, including proliferation-related Notch1, apoptosis-related BCL-2, cell cycle-related CDK6, and EMT-related SMAD4. The oncogene role of SNHG7 in vivo was also confirmed and found that knockdown of SNHG7 delayed the tumor growth with increased miR-34a level and Ki-67 level in OS tissues. These findings demonstrated that the LncRNA SNHG7 is upregulated during the development of OS via inhibition of tumor suppressor miR-34s signals.
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Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/genética , RNA Longo não Codificante/genética , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/metabolismo , TransfecçãoRESUMO
Angelica nitida is an endemic species in China. The complete chloroplast genome sequence of A. nitida was generated by de novo assembly using whole genome next generation sequencing. The complete chloroplast genome was 146,512bp in length and constructed out of four parts - a large single copy (LSC) region of 93,298bp, a small single copy (SSC) region of 18,068bp and two inverted repeat (IRa and IRb) regions of 17,573bp each. The genome annotation predicted a total of 113 genes, including 80 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. Phylogenetic analysis with the reported chloroplast genomes revealed that A. nitida is most closely related to Angelica dahurica.