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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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%).
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.
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.
Heat shock transcription factors (Hsfs) are key regulators in plant heat stress response, and therefore, they play vital roles in signal transduction pathways in response to environmental stresses, ...as well as in plant growth and development.
(Sw.) DC. is an extremophile halophyte with good adaptability to high temperature and salt-drought tolerance, and it can be used as a pioneer species for ecological reconstruction on tropical coral islands. To date, very little is known regarding the functions of
s in the adaptation mechanisms of plant species with specialized habitats, especially in tropical leguminous halophytes. In this study, a genome-wide analysis was performed to identify all the
s in
based on whole-genome sequencing information. The chromosomal location, protein domain or motif organization, and phylogenetic relationships of 28
s were analyzed. Promoter analyses indicated that the expression levels of different
s were precisely regulated. The expression patterns also revealed clear transcriptional changes among different
tissues, indicating that the regulation of
expression varied among organs in a developmental or tissue-specific manner. Furthermore, the expression levels of most
s in response to environmental conditions or abiotic stresses also implied a possible positive regulatory role of this gene family under abiotic stresses, and suggested roles in adaptation to specialized habitats such as tropical coral islands. In addition, some
s were cloned and their possible roles in abiotic stress tolerance were functionally characterized using a yeast expression system. The
s significantly enhanced yeast survival under thermal and oxidative stress challenges. Our results contribute to a better understanding of the plant
gene family and provide a basis for further study of
functions in environmental thermotolerance. Our results also provide valuable information on the evolutionary relationships among
genes and the functional characteristics of the gene family. These findings are beneficial for further research on the natural ecological adaptability of
to tropical environments.
ABSTRACTAlthough 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‐β 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. FASEB J. 33, 10049–10064 (2019). www.fasebj.org
Heat shock protein 20 (Hsp20) is a major family of heat shock proteins that mainly function as molecular chaperones and are markedly accumulated in cells when organisms are subjected to environmental ...stress, particularly heat. Canavalia rosea is an extremophile halophyte with good adaptability to environmental high temperature and is widely distributed in coastal areas or islands in tropical and subtropical regions. In this study, we identified a total of 41 CrHsp20 genes in the C. rosea genome. The gene structures, phylogenetic relationships, chromosome locations, and conserved motifs of each CrHsp20 or encoding protein were analyzed. The promoters of CrHsp20s contained a series of predicted cis-acting elements, which indicates that the expression of different CrHsp20 members is regulated precisely. The expression patterns of the CrHsp20 family were analyzed by RNA sequencing both at the tissue-specific level and under different abiotic stresses, and were further validated by quantitative reverse transcription PCR. The integrated expression profiles of the CrHsp20s indicated that most CrHsp20 genes were greatly upregulated (up to dozens to thousands of times) after 2 h of heat stress. However, some of the heat-upregulated CrHsp20 genes showed completely different expression patterns in response to salt, alkaline, or high osmotic stresses, which indicates their potential specific function in mediating the response of C. rosea to abiotic stresses. In addition, some of CrHsp20s were cloned and functionally characterized for their roles in abiotic stress tolerance in yeast. Taken together, these findings provide a foundation for functionally characterizing Hsp20s to unravel their possible roles in the adaptation of this species to tropical coral reefs. Our results also contribute to the understanding of the complexity of the response of CrHsp20 genes to other abiotic stresses and may help in future studies evaluating the functional characteristics of CrHsp20s for crop genetic improvement.
Display omitted
•First-time achievement of four deep thermal cycles in 7.5 cm2 tubular P-rSOCs.•Preparation of BCZI@LSC air electrodes by a wet chemical method for enhanced TPBs.•An increased current ...density of 51% is achieved by infiltration.•The cell with BCZI + LSC electrode endures 14 reversible cycles for 360 h.•Investigation of degradation mechanisms of two different electrodes.
The electrode microstructure and interface stability play an important role during thermal cycles and reversible cycles for protonic reversible solid oxide cells (P-rSOCs). In this work, the effects of microstructural change of air electrodes on the performance and cycling stability are investigated by using tubular cells with large active area (7.5 cm2). The BaCe0.5Zr0.4In0.1O3@ La0.6Sr0.4CoO3 (BCZI@LSC) composite air electrode is prepared through a wet chemical procedure based on infiltration of the LSC precursor solution into the BCZI electrolyte skeleton. The LSC nanoparticles attach to the electrolyte skeleton in a continuous film-forming morphology, affording abundant three-phase reaction boundaries (TPBs) and the continuous conducting phase. Compared to the BCZI + LSC composite air electrode prepared by conventional mechanical mixing, the cell with the BCZI@LSC electrode demonstrates an increased current density of 51%. The cell with the BCZI + LSC electrode shows acceptable stability during 14 reversible FC-EC cycles and 4 thermal cycles (between 650 °C and room temperature) for 360 h in 20% H2O-air atmosphere. The differences in stability for cells prepared by the two processes are compared and discussed.
Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, ...there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.
(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
. A total of 84
s and three
s were identified in
and classified into nine groups. All CrLEAs and CrASRs harbored the conserved motif for their family proteins. Our results revealed that the
genes were widely distributed in different chromosomes, and all of the
/
genes showed wide expression features in different tissues in
plants. Additionally, we introduced 10 genes from different groups into yeast to assess the functions of the
s/
s. These results contribute to our understanding of
genes from halophytes and provide robust candidate genes for functional investigations in plant species adapted to extreme environments.
PDF
