Identification of cancer prognosis-associated lncRNAs based on the miRNA-TF co-regulatory motifs and dosage sensitivity.

Long non-coding RNAs (lncRNAs) have been shown to be vital players in a majority of physiological and pathological processes, including tumorigenesis and tumor progression. The aim of this study was to identify lncRNAs that can serve as biomarkers for cancer prognosis. Based on dosage sensitivity, we utilized the biological features of known cancer-related lncRNAs, and identified microRNA and transcription factor (miRNA-TF) co-regulatory motifs in an effort to establish a holistic analysis framework and predict new cancer prognosis-associated lncRNAs. We found that lncRNAs with low dosage sensitivity regulated by more than 3 types of co-regulatory motifs were more likely to be associated with cancer. By the use of the integrative analysis of 3035 tumor samples across 9 types of cancer, a total of 33 cancer prognosis-associated lncRNAs were identified. Additionally, on the basis of the miRNA-TF co-regulatory network, we also predicted potential small molecule drugs such as Glucocorticoid and Ginsenoside Rh2 for treating KIRC by targeting miRNA. This study explains the causes of abnormalities in the genome from a new perspective, and provides new clues for cancer diagnosis and prognosis, and research for anti-cancer drugs.

DNA co-methylation analysis of lincRNAs across nine cancer types reveals novel potential epigenetic biomarkers in cancer.

Aim: The potential functions and prognostic value of lincRNAs with co-methylation events are explored in 9 cancer types. Materials & methods: Here, we evaluated the co-methylation events in promoter and gene-body regions between two lincRNAs across 9 cancer types by constructing a systematic biological framework. Results: The co-methylation events in both promoter and gene-body regions tended to be highly cancer specific. Patient samples could be separated by tumor and normal types according to the eigengenes of universal co-methylation clusters. Functional enrichment results revealed the lincRNAs that brought promoter and gene-body co-methylation events that affected cancer progress through participating in different pathways and could serve as potential prognostic biomarkers. Conclusion: The study provides new insight into the epigenetic regulation in cancer and leads to a potential new direction for epigenetic biomarker discovery.

A fluorescence method for homogeneous detection of influenza A DNA sequence based on guanine-quadruplex-N-methylmesoporphyrin IX complex and assistance-DNA inhibition.

In his study, we report a fluorescence method for homogeneous detection of influenza A (H1N1) DNA sequence based on G-quadruplex-NMM complex and assistance-DNA (A-DNA) inhibition. The quadruplex-based functional DNA (QBF-DNA), composed of a complementary probe to the target H1N1 DNA sequence and G-rich fragment, was designed as the signal DNA. The A-DNA consisted of two parts, one part was complementary to target H1N1 DNA and the other part was complementary to the signal DNA. In the absence of target H1N1 DNA, the G-rich fragment of QBF-DNA can form G-quadruplex-NMM complex, which outputted a fluorescent signal. With the presence of target H1N1 DNA, QBF-DNA, and A-DNA can simultaneously hybridize with target H1N1 DNA to form double-helix structure. In this case, the A-DNA partially hybridized with the QBF-DNA, which inhibited the formation of G-quadruplex-NMM complex, leading to the decrease of fluorescent signal. Under the optimum conditions, the fluorescence intensity was inversely proportional to the concentration of target H1N1 DNA over the range from 25 to 700 pmol/L with a detection limit of 8 pmol/L. In addition, the method is target specific and practicability, and would become a new diagnostic assay for H1N1 DNA sequence and other infectious diseases.

Impact of Glyphosate on the Rhizosphere Microbial Communities of An EPSPS-Transgenic Soybean Line ZUTS31 by Metagenome Sequencing.

BACKGROUND: The worldwide use of glyphosate has dramatically increased, but also has been raising concern over its impact on mineral nutrition, plant pathogen, and soil microbiota. To date, the bulk of previous studies still have shown different results on the effect of glyphosate application on soil rhizosphere microbial communities. OBJECTIVE: This study aimed to clarify whether glyphosate has impact on nitrogen-fixation, pathogen or disease suppression, and rhizosphere microbial community of a soybean EPSPS-transgenic line ZUTS31 in one growth season. METHOD: Comparative analysis of the soil rhizosphere microbial communities was performed by 16S rRNA gene amplicons sequencing and shotgun metagenome sequencing analysis between the soybean line ZUTS31 foliar sprayed with diluted glyphosate solution and those sprayed with water only in seed-filling stage. RESULTS: There were no significant differences of alpha diversity but with small and insignificant difference of beta diversity of soybean rhizosphere bacteria after glyphosate treatment. The significantly enriched Gene Ontology (GO) terms were cellular, metabolic, and single-organism of biological process together with binding, catalytic activity of molecular function. The hits and gene abundances of some functional genes being involved in Plant Growth-Promoting Traits (PGPT), especially most of nitrogen fixation genes, significantly decreased in the rhizosphere after glyphosate treatment. CONCLUSION: Our present study indicated that the formulation of glyphosate-isopropylamine salt did not significantly affect the alpha and beta diversity of the rhizobacterial community of the soybean line ZUTS31, whereas it significantly influenced some functional genes involved in PGPT in the rhizosphere during the single growth season.

Effects of an EPSPS-transgenic soybean line ZUTS31 on root-associated bacterial communities during field growth.

The increased worldwide commercial cultivation of transgenic crops during the past 20 years is accompanied with potential effects on the soil microbial communities, because many rhizosphere and endosphere bacteria play important roles in promoting plant health and growth. Previous studies reported that transgenic plants exert differential effects on soil microbial communities, especially rhizobacteria. Thus, this study compared the soybean root-associated bacterial communities between a 5-enolpyruvylshikimate-3-phosphate synthase -transgenic soybean line (ZUTS31 or simply Z31) and its recipient cultivar (Huachun3 or simply HC3) at the vegetative, flowering, and seed-filling stages. High-throughput sequencing of 16S rRNA gene (16S rDNA) V4 hypervariable region amplicons via Illumina MiSeq and real-time quantitative PCR (qPCR) were performed. Our results revealed no significant differences in the overall alpha diversity of root-associated bacterial communities at the three developmental stages and in the beta diversity of root-associated bacterial communities at the flowering stage between Z31 and HC3 under field growth. However, significant differences in the beta diversity of rhizosphere bacterial communities were found at the vegetative and seed-filling stages between the two groups. Furthermore, the results of next generation sequencing and qPCR showed that the relative abundances of root-associated main nitrogen-fixing bacterial genera, especially Bradyrhizobium in the roots, evidently changed from the flowering stage to the seed-filling stage. In conclusion, Z31 exerts transitory effects on the taxonomic diversity of rhizosphere bacterial communities at the vegetative and seed-filling stages compared to the control under field conditions. In addition, soybean developmental change evidently influences the main symbiotic nitrogen-fixing bacterial genera in the roots from the flowering stage to the seed-filling stage.

Identification of cancer-related potential biomarkers based on lncRNA-pseudogene-mRNA competitive networks.

Accumulating evidence indicates that mRNAs and noncoding RNAs act as competitive endogenous RNAs (ceRNAs) and play a key role in tumorigenesis. However, the complex competitive relationship among genes remains unknown. In the present study, the long noncoding RNAs (lncRNAs), pseudogenes and mRNAs that compete with common microRNAs are defined as lncRNA-pseudogene-mRNA competitive triples. We find that some candidate ceRNAs, modules and triples are associated with cancers and can significantly divide patients into high-risk and low-risk groups; thus, they may serve as potential cancer biomarkers. In sum, the present study systematically analyzes the association between competitive triples and cancer, which provides a reference for a deeper understanding of cancer progression.

Integrated analysis of dosage effect lncRNAs in lung adenocarcinoma based on comprehensive network.

Accumulating evidences indicate that cancer-related lncRNAs occur frequent somatic copy number alternation (SCNA). Although individual SCNA lncRNAs have been implicated in tumor biology, their regulatory mechanism has not been assessed in a systematic way. In order to explore the expression characteristics and biological functions of SCNA lncRNAs in cancer, we built a computational framework based on lncRNA expression profiles, lncRNA copy numbers and dosage sensitivity score (DSS). First, we found that the lncRNAs with different DSS were involved in distinct biological processes, while those with the same DSS had similar functions. Second, some of the lncRNAs participated in the progression and metastasis of lung adenocarcinoma (LUAD) through cis-acting regulation. In lncRNA-TF-mRNA network, lncRNAs interacted with 4 TFs and affected the immune system, and further influenced LUAD progression. Third, competing endogenous RNA network analysis inferred that lncRNA ENSG00000240990 competed with HOXA10 to absorb hsa-let-7a/b/f/g-5p and affected patient prognosis in LUAD. Last but not least, by integrating target information of miRNA we also provided a new perspective for the discovery of potential small molecule drugs. In summary, we systematically analyzed the regulatory role of SCNA lncRNAs. This work may facilitate cancer research and serve as the basis for future efforts to understand the role of SCNA lncRNAs, develop novel biomarkers and improve knowledge of tumor biology.

Identification of potential cancer-related pseudogenes in lung adenocarcinoma based on ceRNA hypothesis.

Pseudogenes are initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. Far from being silent, pseudogenes are proved to regulate the expression of protein-coding genes through function as microRNA sponge in vivo. The aim of our study was to propose an integrative systems biology approach to identify disease pseudogenes base on competitive endogenous RNA (ceRNA) hypothesis. Here, we applied our method to lung adenocarcinoma (LUAD) RNASeq data from TCGA and identified 33 candidate pseudogenes. We described the characteristics of the candidate pseudogenes and performed functional enrichment. Through analyzing neighboring genes we found these pseudogenes were surrounded by tumor genes and may involve in tumor pathway. Furthermore, the DNA methylation analysis indicated that 21 pseudogenes co-methylated with their competitive mRNAs. In the co-methylated network, we discovered 6 differentially expressed pseudogenes, which we termed potential LUAD-associated pseudogenes. We further revealed that the 3 ceRNA triples (miR-21-5p-NKAPP1-PRDM11, miR-29c-3p-MSTO2P-EZH2 and miR-29c-3p-RPLP0P2-EZH2), whose high risk groups were associated with the poor prognosis of LUAD, may be considered as potential prognostic signatures. Moreover, by integrating target information of microRNA we also provided a new perspective for the discovery of potential small molecule drugs. This work may facilitate cancer research and serve as the basis for future efforts to understand the role of pseudogenes, develop novel biomarkers and improve knowledge of tumor biology.

The characteristic landscape of lncRNAs classified by RBP-lncRNA interactions across 10 cancers.

RNA-binding proteins (RBPs) are key regulators of gene expression. Some long non-coding RNAs (lncRNAs) affect gene expression by interacting with RBPs. However, whether this influences the biological characteristics of lncRNAs in diseases still remains unknown. Here, we classify lncRNAs into two categories, using the interaction information between lncRNAs and RBPs: the lncRNAs that interact with RBPs (Rlncs) and the lncRNAs that do not interact with RBPs (NRlncs). Then we systematically analyze the basic attributes and functions of the two categories of lncRNAs across 10 cancers. By comparing the two categories, we find that the attributes of Rlncs are significantly higher than those of NRlncs in different aspects such as expression level, protein-coding potential, and evolutionary conservation. Furthermore, functional enrichment analysis reveals that the two categories of lncRNAs are involved in different functions and biological pathways. Finally, the prognostic analysis results suggest that the two categories of lncRNAs affect the overall survival of patients through participating in different functions. Our systematic characterization of Rlncs and NRlncs provides a new perspective for understanding the role of lncRNAs, and improves knowledge of cancer biology.

Impact of a Glyphosate-Tolerant Soybean Line on the Rhizobacteria, Revealed by Illumina MiSeq.

The global commercial cultivation of transgenic crops, including glyphosate-tolerant soybean, has increased widely in recent decades with potential impact on the environment. The bulk of previous studies showed different results on the effects of the release of transgenic plants on the soil microbial community, especially rhizosphere bacteria. In this study, comparative analyses of the bacterial communities in the rhizosphere soils and surrounding soils were performed between the glyphosate-tolerant soybean line NZL06-698 (or simply N698), containing a glyphosate-insensitive EPSPS gene, and its control cultivar Mengdou12 (or simply MD12), by a 16S ribosomal RNA gene (16S rDNA) amplicon sequencing-based Illumina MiSeq platform. No statistically significant difference was found in the overall alpha diversity of the rhizosphere bacterial communities, although the species richness and evenness of the bacteria increased in the rhizosphere of N698 compared with that of MD12. Some influence on phylogenetic diversity of the rhizosphere bacterial communities was found between N698 and MD12 by beta diversity analysis based on weighted UniFrac distance. Furthermore, the relative abundances of part rhizosphere bacterial phyla and genera, which included some nitrogen-fixing bacteria, were significantly different between N698 and MD12. Our present results indicate some impact of the glyphosate-tolerant soybean line N698 on the phylogenetic diversity of rhizosphere bacterial communities together with a significant difference in the relative abundances of part rhizosphere bacteria at different classification levels as compared with its control cultivar MD12, when a comparative analysis of surrounding soils between N698 and MD12 was used as a systematic contrast study.

Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAF(V600E) inhibitors.

A series of novel 5-phenyl-1H-pyrazole derivatives (5 a-5 u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 µM for BRAF(V600E). Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 µM, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.

Comparative population genomics reveals the domestication history of the peach, Prunus persica, and human influences on perennial fruit crops.

BACKGROUND: Recently, many studies utilizing next generation sequencing have investigated plant evolution and domestication in annual crops. Peach, Prunus persica, is a typical perennial fruit crop that has ornamental and edible varieties. Unlike other fruit crops, cultivated peach includes a large number of phenotypes but few polymorphisms. In this study, we explore the genetic basis of domestication in peach and the influence of humans on its evolution. RESULTS: We perform large-scale resequencing of 10 wild and 74 cultivated peach varieties, including 9 ornamental, 23 breeding, and 42 landrace lines. We identify 4.6 million SNPs, a large number of which could explain the phenotypic variation in cultivated peach. Population analysis shows a single domestication event, the speciation of P. persica from wild peach. Ornamental and edible peach both belong to P. persica, along with another geographically separated subgroup, Prunus ferganensis. CONCLUSIONS: Our analyses enhance our knowledge of the domestication history of perennial fruit crops, and the dataset we generated could be useful for future research on comparative population genomics.

Impact of Next-Generation Sequencing (NGS) technology on cardiovascular disease research.

In recent years, hundreds of gene loci associated with multiple cardiovascular pathologies and traits have been identified through high-throughput Next-Generation Sequencing (NGS) technology. Due to the increasing efficiency and decreasing cost of NGS, rapid progresses anticipated in the field of CVD research. This review summarizes the main strategies of CV research with NGS at the level of genomics, transcriptomics, epigenetics, and proteomics.

[Form deprivation myopia in C57BL/6 mice].

OBJECTIVE: To investigate the changes of refraction and ocular biometric parameters in form deprived myopia, and try to find the effective duration to induce significant myopic shift in C57BL/6 mice. METHODS: It was an experimental study. Seventy-four C57BL/6 mice, approximately 23 days old, were divided into three groups randomly: FD (Form-deprivation), Recovery and Normal control groups. FD group was treated with diffuser worn on one eye for 2 weeks (n = 12), 3 weeks (n = 20) and 4 weeks (n = 18), respectively. In Recovery group, diffusers were removed after 4 weeks form deprivation, and vertical meridian refraction and other biometric parameters were performed immediately on 4(th) and 7(th) day. The same measurements were performed in the normal control group at the same time-points. Refraction was measured by photoretinoscopy and corneal radius of curvature (CRC) was measured by a modified keratometry. Corneal thickness (CT), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL) were measured by optical coherence tomography (OCT) with focal plane advancement. RESULTS: The FD eyes were approximately -0.85 D more myopic compared to the fellow and the normal control eyes after 2 weeks form deprivation (P > 0.05). After 3 weeks form deprivation, treated eye had a obvious myopic shift (about -4.27 D) compared to fellow eye, with increased vitreous chamber depth and axial length, however, there was no statistic difference among FD eye, fellow eye and control eye. And after 4 weeks form deprivation, treated eyes were induced significant myopic shift (about -5.22 D) compared with the fellow eye. The difference in refraction of form-deprived and fellow eyes was significantly correlated with the difference in vitreous chamber depth and axial length, which indicate that the induced myopia was mainly axial. The relative myopia shifted rapidly diminished in 4 days after removing the diffuser, followed by a slower recovery. A complete refraction recovery occurred by 7 days after removal of the diffuser compared to the fellow and normal control eyes (P > 0.05). CONCLUSION: Form deprivation myopia can be induced in C57BL/6 mice, but it required longer period than other animals; A complete recovery occurred by 7 days after removal of the diffuser.Optical Coherence Tomography is a useful instrument to measure mouse eye dimension.