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1.
Brief Bioinform ; 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415289

RESUMO

Circular RNAs (circRNAs) are widely expressed in highly diverged eukaryotes. Although circRNAs have been known for many years, their function remains unclear. Interaction with RNA-binding protein (RBP) to influence post-transcriptional regulation is considered to be an important pathway for circRNA function, such as acting as an oncogenic RBP sponge to inhibit cancer. In this study, we design a deep learning framework, CRPBsites, to predict the binding sites of RBPs on circRNAs. In this model, the sequences of variable-length binding sites are transformed into embedding vectors by word2vec model. Bidirectional LSTM is used to encode the embedding vectors of binding sites, and then they are fed into another LSTM decoder for decoding and classification tasks. To train and test the model, we construct four datasets that contain sequences of variable-length binding sites on circRNAs, and each set corresponds to an RBP, which is overexpressed in bladder cancer tissues. Experimental results on four datasets and comparison with other existing models show that CRPBsites has superior performance. Afterwards, we found that there were highly similar binding motifs in the four binding site datasets. Finally, we applied well-trained CRPBsites to identify the binding sites of IGF2BP1 on circCDYL, and the results proved the effectiveness of this method. In conclusion, CRPBsites is an effective prediction model for circRNA-RBP interaction site identification. We hope that CRPBsites can provide valuable guidance for experimental studies on the influence of circRNA on post-transcriptional regulation.

2.
BMC Plant Biol ; 21(1): 333, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256694

RESUMO

BACKGROUND: Canavalia rosea (Sw.) DC. (bay bean) is an extremophile halophyte that is widely distributed in coastal areas of the tropics and subtropics. Seawater and drought tolerance in this species may be facilitated by aquaporins (AQPs), channel proteins that transport water and small molecules across cell membranes and thereby maintain cellular water homeostasis in the face of abiotic stress. In C. rosea, AQP diversity, protein features, and their biological functions are still largely unknown. RESULTS: We describe the action of AQPs in C. rosea using evolutionary analyses coupled with promoter and expression analyses. A total of 37 AQPs were identified in the C. rosea genome and classified into five subgroups: 11 plasma membrane intrinsic proteins, 10 tonoplast intrinsic proteins, 11 Nod26-like intrinsic proteins, 4 small and basic intrinsic proteins, and 1 X-intrinsic protein. Analysis of RNA-Seq data and targeted qPCR revealed organ-specific expression of aquaporin genes and the involvement of some AQP members in adaptation of C. rosea to extreme coral reef environments. We also analyzed C. rosea sequences for phylogeny reconstruction, protein modeling, cellular localizations, and promoter analysis. Furthermore, one of PIP1 gene, CrPIP1;5, was identified as functional using a yeast expression system and transgenic overexpression in Arabidopsis. CONCLUSIONS: Our results indicate that AQPs play an important role in C. rosea responses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role AQPs play in mediating C. rosea adaptation to extreme environments, but also improve our knowledge of plant aquaporin evolution more generally.


Assuntos
Aquaporinas/genética , Canavalia/genética , Secas , Solo/química , Adaptação Fisiológica , Motivos de Aminoácidos , Aquaporinas/fisiologia , Evolução Biológica , Canavalia/fisiologia , Mapeamento Cromossômico , Cromossomos de Plantas , Ecossistema , Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , RNA-Seq , Estresse Fisiológico , Transcriptoma
3.
Genomics ; 113(5): 3072-3082, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34246693

RESUMO

Rubiaceae is the fourth largest and a taxonomically complex family of angiosperms. Many species in this family harbor low reproductive isolation and frequently exhibit inconsistent phenotypic characteristics. Therefore, taxonomic classification and their phylogenetic relationships in the Rubiaceae family is challenging, especially in the genus Leptodermis. Considering the low taxonomic confusion and wide distribution, Leptodermis oblonga is selected as a representative Leptodermis for genome sequencing. The assemblies resulted in 497 Mbp nuclear and 155,100 bp chloroplast genomes, respectively. Using the nuclear genome as a reference, SNPs were called from 37 Leptodermis species or varieties. The phylogenetic tree based on SNPs exhibited high resolution for species delimitation of the complex and well-resolved phylogenetic relationships in the genus. Moreover, 28,987 genes were predicted in the nuclear genome and used for comparative genomics study. As the first chromosomal-level genome of the subfamily Rubioideae in Rubiaceae, it will provide fruitfully evolutionary understanding in the family.

4.
Genomics ; 113(4): 2537-2546, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34089785

RESUMO

Puya raimondii, the Queen of the Andes, is an endangered high Andean species in the Bromeliaceae family. Here, we report its first genome to promote its conservation and evolutionary study. Comparative genomics showed P. raimondii diverged from Ananas comosus about 14.8 million years ago, and the long terminal repeats were likely to contribute to the genus diversification in last 3.5 million years. The gene families related to plant reproductive development and stress responses significantly expanded in the genome. At the same time, gene families involved in disease defense, photosynthesis and carbohydrate metabolism significantly contracted, which may be an evolutionary strategy to adapt to the harsh conditions in high Andes. The demographic history analysis revealed the P. raimondii population size sharply declined in the Pleistocene and then increased in the Holocene. We also designed and tested 46 pairs of universal primers for amplifying orthologous single-copy nuclear genes in Puya species.

5.
Gene ; 791: 145715, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33984444

RESUMO

Leptodermis scabrida complex is one of the important components of genus Leptodermis, which is mainly distributed in the Himalaya Mountains. It includes species of L. gracilis, L. hirsutiflora, L. hirsutiflora var. ciliata, L. kumaonensis, L. pilosa var. acanthoclada and L. scabrida. However, species boundaries and relationships within this complex are unclear based on current morphological and molecular evidence. We sequenced 13 complete chloroplast (cp) genomes representing seven taxa of the complex and two non-Leptodermis scabrida complex taxa. After de novo assembly and annotation, we performed comparative genomic analysis. All cp genomes showed highly conserved structures, and the genome sizes ranged from 154,369 bp to 154,885 bp and possessed the same GC content (37.5%). A total of 113 unique genes were identified in each cp sample, including 79 protein coding genes, 30 tRNAs, and four rRNAs. Repeat sequences and SSRs were detected, showing great similarity among all taxa in this complex. Six highly variable regions, including trnS-trnG, rps2-rpoC2, ndhF, rpl32-ccsA, ccsA-ndhD, and ndhA, were screened as potential molecular markers for phylogenetic reconstruction. Based on a total of 27 complete cp genome sequences, the consistent and robust phylogenetic relationships were firstly constructed and the same species within L. scabrida complex clustered into a group. The divergence time of Leptodermis from ancestral taxa occurred at the middle Eocene, which might be due to geological and climatic changes. The 13 complete cp genome sequences reported will provide new clues for phylogeny elucidation, species identification and evolutionary history speculation of Leptodermis, as well as in Rubiaceae.


Assuntos
Genoma de Cloroplastos/genética , Rubiaceae/genética , Composição de Bases/genética , Cloroplastos/genética , Cloroplastos/metabolismo , Evolução Molecular , Tamanho do Genoma/genética , Genômica/métodos , Repetições de Microssatélites/genética , Filogenia , RNA Ribossômico/genética , Rubiaceae/metabolismo , Sequenciamento Completo do Genoma
6.
J Cell Mol Med ; 25(10): 4671-4683, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33811437

RESUMO

Clinical and experimental evidence indicates that tumour-associated macrophages support cancer progression. Moreover, macrophage-derived extracellular vesicles (EVs) are involved in pathogenesis of multiple cancers, yet the functions of molecular determinants in which have not been fully understood. Herein, we aim to understand whether macrophage modulates pancreatic ductal adenocarcinoma (PDAC) progression in an EV-dependent manner and the underlying mechanisms. microRNA (miR)-365 was experimentally determined to be enriched in the EVs from M2 macrophages (M2-EVs), which could be transferred into PDAC cells. Using a co-culture system, M2-EVs could enhance the proliferating, migrating and invading potentials of PDAC cells, while inhibition of miR-365 in M2-EVs could repress these malignant functions. B-cell translocation gene 2 (BTG2) was identified to be a direct target of miR-365, while the focal adhesion kinase (F/ATP)-dependent tyrosine kinase (AKT) pathway was activated by miR-365. We further demonstrated that overexpression of BTG2 could delay the progression of PDAC in vitro, whereas by impairing BTG2-mediated anti-tumour effect, M2-EV-miR-365 promoted PDAC progression. For validation, a nude mouse model of tumorigenesis was established, in which we found that targeting M2-EV-miR-365 contributed to suppression of tumour growth. Collectively, M2-EVs carry miR-365 to suppress BTG2 expression, which activated FAK/AKT pathway, thus promoting PDAC development.


Assuntos
Vesículas Extracelulares/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Imediatamente Precoces/metabolismo , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Proliferação de Células , Quinase 1 de Adesão Focal/genética , Humanos , Proteínas Imediatamente Precoces/genética , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925342

RESUMO

Canavalia rosea (bay bean), distributing in coastal areas or islands in tropical and subtropical regions, is an extremophile halophyte with good adaptability to seawater and drought. Late embryogenesis abundant (LEA) proteins typically accumulate in response to various abiotic stresses, including dehydration, salinity, high temperature, and cold, or during the late stage of seed development. Abscisic acid-, stress-, and ripening-induced (ASR) genes are stress and developmentally regulated plant-specific genes. In this study, we reported the first comprehensive survey of the LEA and ASR gene superfamily in C. rosea. A total of 84 CrLEAs and three CrASRs were identified in C. rosea and classified into nine groups. All CrLEAs and CrASRs harbored the conserved motif for their family proteins. Our results revealed that the CrLEA genes were widely distributed in different chromosomes, and all of the CrLEA/CrASR genes showed wide expression features in different tissues in C. rosea plants. Additionally, we introduced 10 genes from different groups into yeast to assess the functions of the CrLEAs/CrASRs. These results contribute to our understanding of LEA/ASR genes from halophytes and provide robust candidate genes for functional investigations in plant species adapted to extreme environments.


Assuntos
Canavalia/genética , Canavalia/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Adaptação Fisiológica/genética , Canavalia/crescimento & desenvolvimento , China , Secas , Regulação da Expressão Gênica de Plantas/genética , Genoma de Planta/genética , Filogenia , Proteínas de Plantas/metabolismo , Salinidade , Tolerância ao Sal/genética , Plantas Tolerantes a Sal/metabolismo , Sementes/metabolismo , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia
8.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429984

RESUMO

Aquaporins are channel proteins that facilitate the transmembrane transport of water and other small neutral molecules, thereby playing vital roles in maintaining water and nutrition homeostasis in the life activities of all organisms. Canavalia rosea, a seashore and mangrove-accompanied halophyte with strong adaptability to adversity in tropical and subtropical regions, is a good model for studying the molecular mechanisms underlying extreme saline-alkaline and drought stress tolerance in leguminous plants. In this study, a PIP2 gene (CrPIP2;3) was cloned from C. rosea, and its expression patterns and physiological roles in yeast and Arabidopsis thaliana heterologous expression systems under high salt-alkali and high osmotic stress conditions were examined. The expression of CrPIP2;3 at the transcriptional level in C. rosea was affected by high salinity and alkali, high osmotic stress, and abscisic acid treatment. In yeast, the expression of CrPIP2;3 enhanced salt/osmotic and oxidative sensitivity under high salt/osmotic and H2O2 stress. The overexpression of CrPIP2;3 in A. thaliana could enhance the survival and recovery of transgenic plants under drought stress, and the seed germination and seedling growth of the CrPIP2;3 OX (over-expression) lines showed slightly stronger tolerance to high salt/alkali than the wild-type. The transgenic plants also showed a higher response level to high-salinity and dehydration than the wild-type, mostly based on the up-regulated expression of salt/dehydration marker genes in A. thaliana plants. The reactive oxygen species (ROS) staining results indicated that the transgenic lines did not possess stronger ROS scavenging ability and stress tolerance than the wild-type under multiple stresses. The results confirmed that CrPIP2;3 is involved in the response of C. rosea to salt and drought, and primarily acts by mediating water homeostasis rather than by acting as an ROS transporter, thereby influencing physiological processes under various abiotic stresses in plants.


Assuntos
Arabidopsis/genética , Canavalia/genética , Plantas Tolerantes a Sal/genética , Estresse Fisiológico/genética , Álcalis/toxicidade , Arabidopsis/crescimento & desenvolvimento , Canavalia/crescimento & desenvolvimento , Secas , Regulação da Expressão Gênica de Plantas , Germinação/efeitos dos fármacos , Peróxido de Hidrogênio/química , Pressão Osmótica/efeitos dos fármacos , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Salinidade , Tolerância ao Sal/genética , Plântula/efeitos dos fármacos , Cloreto de Sódio/toxicidade
9.
BMC Bioinformatics ; 22(1): 19, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413092

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are widely expressed in cells and tissues and are involved in biological processes and human diseases. Recent studies have demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which is considered an important aspect for investigating the function of circRNAs. RESULTS: In this study, we design a slight variant of the capsule network, called circRB, to identify the sequence specificities of circRNAs binding to RBPs. In this model, the sequence features of circRNAs are extracted by convolution operations, and then, two dynamic routing algorithms in a capsule network are employed to discriminate between different binding sites by analysing the convolution features of binding sites. The experimental results show that the circRB method outperforms the existing computational methods. Afterwards, the trained models are applied to detect the sequence motifs on the seven circRNA-RBP bound sequence datasets and matched to known human RNA motifs. Some motifs on circular RNAs overlap with those on linear RNAs. Finally, we also predict binding sites on the reported full-length sequences of circRNAs interacting with RBPs, attempting to assist current studies. We hope that our model will contribute to better understanding the mechanisms of the interactions between RBPs and circRNAs. CONCLUSION: In view of the poor studies about the sequence specificities of circRNA-binding proteins, we designed a classification framework called circRB based on the capsule network. The results show that the circRB method is an effective method, and it achieves higher prediction accuracy than other methods.


Assuntos
Biologia Computacional/métodos , RNA Circular , Algoritmos , Sítios de Ligação , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Proteínas de Ligação a RNA
11.
Endoscopy ; 52(11): 1004-1013, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869230

RESUMO

BACKGROUND: Lack of forward-viewing endoscopy experience impairs training in endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the effect of ERCP mechanical simulator (EMS) practice on ERCP performance by surgical trainees. PATIENTS AND METHODS: 12 surgical trainees without endoscopy experience were randomly allocated to non-EMS (n = 6) programs or to EMS (n = 6) programs with coaching and 20 hours of supervised EMS practice. All trainees then received supervised hands-on clinical ERCP training. Trainers provided verbal instructions and hands-on assistance, and took over if cannulation was not achieved by 20 minutes. Blinded trainers rated clinical performance. RESULTS: Each group performed 150 clinical ERCPs. Biliary cannulation success was significantly higher in the EMS vs. the non-EMS group (P = 0.006), with shorter mean times (in minutes) for intubation, cannulation, and completion (all P < 0.001). EMS trainees showed a significantly better mean performance score (P = 0.006). In multivariate analysis, after adjusting for case sequence, CBD stone, complexity, and EMS training, the effect of EMS practice on odds for successful cannulation remained highly significant (odds ratio [OR] 2.10 [95 %CI 1.46 - 3.01]). At 6 months EMS trainees still had better cannulation success vs. non-EMS controls (P = 0.045); no difference was observed after 1 year. CONCLUSIONS: EMS practice shortens the ERCP early learning curve of inexperienced surgical trainees, improves clinical success in selective biliary cannulation, and may reduce complications.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Competência Clínica , Cateterismo , Humanos , Curva de Aprendizado
12.
World J Gastroenterol ; 26(19): 2403-2415, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476801

RESUMO

BACKGROUND: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM: To verify the clinical value of our newly proposed PAD classification. METHODS: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.


Assuntos
Ampola Hepatopancreática/patologia , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Divertículo/cirurgia , Duodenopatias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Ampola Hepatopancreática/cirurgia , Cateterismo/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Divertículo/diagnóstico , Divertículo/patologia , Duodenopatias/diagnóstico , Duodenopatias/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
BMC Bioinformatics ; 21(1): 229, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503474

RESUMO

BACKGROUND: Circular RNA (circRNA) has been extensively identified in cells and tissues, and plays crucial roles in human diseases and biological processes. circRNA could act as dynamic scaffolding molecules that modulate protein-protein interactions. The interactions between circRNA and RNA Binding Proteins (RBPs) are also deemed to an essential element underlying the functions of circRNA. Considering cost-heavy and labor-intensive aspects of these biological experimental technologies, instead, the high-throughput experimental data has enabled the large-scale prediction and analysis of circRNA-RBP interactions. RESULTS: A computational framework is constructed by employing Positive Unlabeled learning (P-U learning) to predict unknown circRNA-RBP interaction pairs with kernel model MFNN (Matrix Factorization with Neural Networks). The neural network is employed to extract the latent factors of circRNA and RBP in the interaction matrix, the P-U learning strategy is applied to alleviate the imbalanced characteristics of data samples and predict unknown interaction pairs. For this purpose, the known circRNA-RBP interaction data samples are collected from the circRNAs in cancer cell lines database (CircRic), and the circRNA-RBP interaction matrix is constructed as the input of the model. The experimental results show that kernel MFNN outperforms the other deep kernel models. Interestingly, it is found that the deeper of hidden layers in neural network framework does not mean the better in our model. Finally, the unlabeled interactions are scored using P-U learning with MFNN kernel, and the predicted interaction pairs are matched to the known interactions database. The results indicate that our method is an effective model to analyze the circRNA-RBP interactions. CONCLUSION: For a poorly studied circRNA-RBP interactions, we design a prediction framework only based on interaction matrix by employing matrix factorization and neural network. We demonstrate that MFNN achieves higher prediction accuracy, and it is an effective method.


Assuntos
Redes Neurais de Computação , RNA Circular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Área Sob a Curva , Linhagem Celular Tumoral , Bases de Dados Factuais , Humanos , Neoplasias/genética , Neoplasias/patologia , Curva ROC
14.
Onco Targets Ther ; 13: 2469-2481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273719

RESUMO

Background: Several studies have indicated that the anoikis effector Bcl-2 inhibitor of transcription 1 (Bit1) can promote or inhibit tumor progression depending on the nature of the malignancy. However, its regulatory effects on gliomas are unknown. Methods: This study aimed at assessing Bit1 expression in glioma tissues and cells, its subsequent effects on glioma cell apoptosis, proliferation, invasion, and migration, and the underlying molecular mechanisms. Results: The findings showed that lower Bit1 expressions in glioma tissues as well as a negative correlation between Bit1 expression and glioma grade. Additional findings also revealed that Bit1 silencing significantly inhibited anoikis and enhanced glioma cell proliferation, invasion, and migration. Further analysis showed that the decrease in Bit1 expressions led to malignancy proliferation and anoikis resistance through activation of the IL-6/STAT3 signaling pathway. Conclusion: Our data suggested that Bit1 may play an anti-oncogenic role in glioma cells and that a decrease in its expressions might induce glioma cell proliferation, migration, and invasion through the IL-6/STAT3 signaling pathway.

15.
Artif Cells Nanomed Biotechnol ; 48(1): 415-424, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31914803

RESUMO

Objective: To investigate the effects of microRNA-142-3p (miR-142-3p) on the biological characteristics of pancreatic cancer cells and its mechanism.Methods: The expression of miR-142-3p and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) in pancreatic tissues and four cancer cell lines (Panc-1, BxPC-3, AsPC-1, MIA-PaCa2) were detected by Quantitative PCR (qPCR) or Western blot. The cell viability of pancreatic cancer cells was examined by MTT assay. The apoptosis of pancreatic cancer cells was measured by flow cytometry. Transwell assay was utilized to test the migration and invasion of pancreatic cancer cells. Bioinformatics analysis for miR-142-3p was conducted and the dual luciferase reporter gene assay was utilized to further validate the predicted target relationship. The protein levels of PI3K, p-AKT and T-AKT were analyzed by Western blot.Results: The expression of miR-142-3p was down-regulated, while the expression of NUCKS1 was significantly up-regulated in pancreatic tissues and four cancer cell lines. The expression of miR-142-3p in pancreatic tissues was inversely correlated with NUCKS1 expression. Overexpression of miR-142-3p inhibited the cell viability, cell migration, and invasion, while promoted cell apoptosis of AsPC-1 and MIA-PaCa2 cells. MiR-142-3p targeted NUCKS1 and negatively regulated NUCKS1. Overexpression of miR-142-3p decreased PI3K and p-AKT expression. Up-regulation of NUCKS1 partially reversed the effects of the overexpression of miR-142-3p on the cell viability, cell apoptosis, migration and invasion, as well as PI3K and p-AKT expression in AsPC-1 and MIA-PaCa2 cells.Conclusion: MiR-142-3p regulated the biological characteristics of pancreatic cancer cells by directly targeting NUCKS1.

16.
Angew Chem Int Ed Engl ; 59(9): 3699-3704, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31851408

RESUMO

Solid-state Li metal batteries (SSLMBs) have attracted considerable interests due to their promising energy density as well as high safety. However, the realization of a well-matched Li metal/solid-state electrolyte (SSE) interface remains challenging. Herein, we report g-C3 N4 as a new interface enabler. We discover that introducing g-C3 N4 into Li metal can not only convert the Li metal/garnet-type SSE interface from point contact to intimate contact but also greatly enhance the capability to suppress the dendritic Li formation because of the greatly enhanced viscosity, decreased surface tension of molten Li, and the in situ formation of Li3 N at the interface. Thus, the resulting Li-C3 N4 |SSE|Li-C3 N4 symmetric cell gives a significantly low interfacial resistance of 11â€…Ω cm2 and a high critical current density (CCD) of 1500 µA cm-2 . In contrast, the same symmetric cell configuration with pristine Li metal electrodes has a much larger interfacial resistance (428â€…Ω cm2 ) and a much lower CCD (50 µA cm-2 ).

17.
Life Sci ; 239: 117013, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678287

RESUMO

AIMS: Liver cancer is one of the leading causes of cancer mortality worldwide. Inspired by the biological structure and function of low-density lipoprotein (LDL), in this study, an ApopB-100 based targeted lipid nanoparticles was synthesized to improve the therapeutic efficacy in liver cancer treatment. MAIN METHODS: The biological composition of ApopB is similar to LDL which can effectively increase the targeting efficiency of nanoparticles in LDL receptor (LDLR)-overexpressed liver tumors. KEYFINDINGS: We have demonstrated that the co-administration of sorafenib (SRF) and Dihydroartemisinin (DHA) could exhibit synergistic anticancer effect in HepG2 liver cancer cells. DHA produced excessive cellular reactive oxygen species (ROS) and induced greater apoptosis of cancer cells. LDL-based SRF/DHA-loaded lipid nanoparticles (LD-SDN) showed remarkable decrease in the cell viability compared to that of either of single drug treated cancer cells. Combination of SRF+DHA resulted in predominant SubG1 proportion of cells. LD-SDN exhibited the highest SubG1 (%) of cells compared to that of any of the individual drugs. Most importantly, robust antitumor response and delayed tumor growth was observed for LD-SDN treated xenograft tumor model. Ki67 proliferation index of LD-SDN (22.1 ± 5.6%) is significantly lesser compared to that of either control (86.2 ± 6.9%) or SRF (75.4 ± 4.89%) or DHA (69.4 ± 6.9%). SIGNIFICANCES: These data provide strong evidence that LDL-mimetic lipid nanoformulations could be utilized as a biocompatible and tumor targeted platform for the delivery of multiple anticancer drugs in cancer treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Lipídeos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas , Receptores de LDL/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Artemisininas/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe/administração & dosagem
18.
Molecules ; 24(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703384

RESUMO

Circular RNAs (circRNAs) are extensively expressed in cells and tissues, and play crucial roles in human diseases and biological processes. Recent studies have reported that circRNAs could function as RNA binding protein (RBP) sponges, meanwhile RBPs can also be involved in back-splicing. The interaction with RBPs is also considered an important factor for investigating the function of circRNAs. Hence, it is necessary to understand the interaction mechanisms of circRNAs and RBPs, especially in human cancers. Here, we present a novel method based on deep learning to identify cancer-specific circRNA-RBP binding sites (CSCRSites), only using the nucleotide sequences as the input. In CSCRSites, an architecture with multiple convolution layers is utilized to detect the features of the raw circRNA sequence fragments, and further identify the binding sites through a fully connected layer with the softmax output. The experimental results show that CSCRSites outperform the conventional machine learning classifiers and some representative deep learning methods on the benchmark data. In addition, the features learnt by CSCRSites are converted to sequence motifs, some of which can match to human known RNA motifs involved in human diseases, especially cancer. Therefore, as a deep learning-based tool, CSCRSites could significantly contribute to the function analysis of cancer-associated circRNAs.


Assuntos
Bases de Dados de Proteínas , Aprendizado Profundo , Proteínas de Neoplasias , Neoplasias , RNA Circular , RNA Neoplásico , Proteínas de Ligação a RNA , Análise de Sequência de Proteína , Sítios de Ligação , Humanos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/química , Neoplasias/genética , Neoplasias/metabolismo , RNA Circular/química , RNA Circular/genética , RNA Circular/metabolismo , RNA Neoplásico/química , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
19.
Pharm Res ; 36(10): 145, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396764

RESUMO

PURPOSE: The immediate plasma metabolism and development of chemo-resistance (single agent) severely hampers the clinical effectiveness of Sorafenib (SRF) in liver cancer therapy. MicroRNA27a inhibition is a promising biological strategy for breast cancer therapy. METHODS: In this study, we aimed to prepare SRF and anti-miRNA27a-loaded anti-GPC3 antibody targeted lipid nanoparticles to enhance the therapeutic efficacy against liver cancers. In this study, we have employed a unique cationic switchable lipid (CSL) as a mean to encapsulate miRNA as well as to confer pH-responsiveness to the nanocarrier system. RESULTS: The G-S27LN was nanosized and offered a pH-responsive release of SRF from the carrier system and we have demonstrated the specific affinity of G-S27LN towards the GPC3-overexpressed HepG2 cancer cells. Anti-microRNA27a significantly increased the protein expression of FOXO1 and PPAR-γ which are crucial components involved in proliferation and apoptosis of tumor cells. Combination of SRF and anti-miRNA27a (G-S27LN) resulted in significantly lower cell viability with a marked increase in the apoptosis cell proportion compared to that of free SRF indicating the synergistic anticancer effect. Animal studies in liver cancer xenograft model demonstrated significant suppression of tumor burden, reduced tumor cell and elevated TUNEL positive apoptosis with no toxicity concerns in animals treated with G-S27LN formulation. CONCLUSION: The CSL-based G-S27LN efficiently co-delivered anti-microRNA27a and SRF and therefore represents a promising therapy to treat liver cancer. This study also brings forth a platform strategy for the effective treatment of number of other advanced cancers.


Assuntos
Antagomirs/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Glipicanas/imunologia , Lipídeos/química , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/imunologia , Nanopartículas/química , Sorafenibe/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/química , Sinergismo Farmacológico , Proteína Forkhead Box O1/metabolismo , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Camundongos Nus , PPAR gama/metabolismo , Fosforilcolina/química , Polietilenoglicóis/química
20.
FASEB J ; 33(9): 10049-10064, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31199671

RESUMO

Although the role of the Hippo signaling pathway in development and tumorigenesis has been extensively studied in multiple organs, its role in ovarian follicle development remains largely unknown. Here, we report that Yes-Associated Protein 1 (YAP1), the major effector of Hippo signaling, is spatiotemporally expressed in ovarian granulosa cells and plays a critical role in the regulation of follicle development. We found that the active form of YAP1 (nuclear YAP1) was predominantly expressed in proliferative granulosa cells, whereas the inactive form of YAP1 (cytoplasmic YAP1) was mainly detected in luteal cells (terminally differentiated granulosa cells). Pharmacological inhibition of YAP1 activity disrupted mouse ovarian follicle development in vitro and in vivo. Foxl2 promoter-driven knockout of Yap1 in ovarian granulosa cells resulted in increased apoptosis of granulosa cells, decreased number of corpora lutea, reduced ovarian size, and subfertility in transgenic mice. However, Cyp19a1 promoter-driven knockout of Yap1 in differentiated granulosa cells of preovulatory follicles and luteal cells of corpora lutea had no effect on ovarian morphology and fertility. Mechanistic studies demonstrated that YAP1 interacted with epidermal growth factor receptor and TGF-ß signaling pathways to regulate granulosa cell proliferation, differentiation, and survival. Results from this study identify YAP1 as a critical regulator of granulosa cell proliferation and differentiation. Balanced expression and activation of YAP1 is essential for follicle development and successful reproduction. YAP1 is a promising target for treatment of subfertility associated with abnormal granulosa cell function.-Lv, X., He, C., Huang, C., Wang, H., Hua, G., Wang, Z., Zhou, J., Chen, X., Ma, B., Timm, B. K., Maclin, V., Dong, J., Rueda, B. R., Davis, J. S., Wang, C. Timely expression and activation of YAP1 in granulosa cells is essential for ovarian follicle development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas de Ciclo Celular/fisiologia , Células da Granulosa/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Animais , Aromatase/genética , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/genética , Diferenciação Celular , Divisão Celular , Linhagem Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Receptores ErbB/metabolismo , Feminino , Proteína Forkhead Box L2/genética , Técnicas de Inativação de Genes , Genes Sintéticos , Células da Granulosa/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Folículo Ovariano/citologia , Folículo Ovariano/metabolismo , Regiões Promotoras Genéticas , Transporte Proteico , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Recombinantes/metabolismo , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/fisiologia , Verteporfina/farmacologia
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