Search

Long interspersed nuclear elements (LINEs) play essential role in shaping chromatin state, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form into a gel-like meshwork via phase-separation, providing a partially dynamic platform for chromatin spatial organization. Either depletion of MATR3 or AS L1 RNAs changes nuclear distribution of each other and leads to chromatin reorganization in the nucleus. After MATR3 depletion, topologically associating domains (TADs) that highly transcribed MATR3-associated AS L1 RNAs showed a decrease on local chromatin interactions. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause chromatin reorganization. Collectively, we revealed an essential role of meshwork formed by nuclear matrix and retrotransposon-derived RNAs in gathering chromatin in the nucleus.

Objectives We aimed to evaluate whether carboplatin has a comparable efficacy with cisplatin as part of weekly concurrent chemoradiotherapy for cervical cancer (Car-RT vs. Cis-RT). Methods A literature search was conducted and both prospective and retrospective studies that evaluated the efficacy of Car-RT for cervical cancer were included. The primary endpoints were complete response (CR) rate, progression-free survival (PFS)/disease-free survival (DFS), overall survival (OS), reported as odds ratios (ORs) and 95% confidence intervals (CIs). The estimated CR rate and survival of patients treated with Car-RT were pooled. Acute toxicity was also summarized. Results Twelve studies consisting of 1698 patients were eligible for meta-analysis. A lower CR rate (OR, 0.53; 95% CI, 0.34–0.82, I2 = 0%) and a trend toward poorer 3-year PFS/DFS (OR, 0.71; 95% CI, 0.49–1.02, I2 = 0%) and 3-year OS (OR, 0.70; 95% CI, 0.46–1.05, I2 = 36%) were found in Car-RT compared with Cis-RT. For the Car-RT groups, the pooled overall CR rate was 81% (95% CI 0.74–0.89). The pooled 3-year PFS/DFS rate was 64% (95% CI 0.52–0.78). The pooled 3-year OS rate was 73% (95% CI 0.62–0.87). Acute toxic events ≥ grade 3 were infrequent in the Car-RT groups. Conclusions Car-RT showed a poorer tumor response and a trend toward inferior survival compared with Cis-RT in the treatment of cervical cancer. However, this evidence was limited by the imbalance among studies. Due to the encouraging efficacy and low toxicity, carboplatin is a suitable concurrent agent for patients with contraindications to cisplatin.

To solve the problems that the position error of the classcial DV-Hop localization algorithm is too large to satisfy the precision requirements of node positioning ,this paper put forward an imporved algorithm. Firstly, the algorithm introduces the dual communication radius method. Through the method of two broadcasts, the calculation method of the minimum hops is improved, and the minimum hops between nodes is further refined. Secondly, the usage of the particle swarm optimization algorithm can reduce the error when using the least squares method to compute the coordinate of unknown node. By using the improved particle swarm optimization algorithm, the large error of the least squares method for solving the unknown node coordinates is optimized, and then, make some improvements to avoid the standard particle swarm optimization algorithm fall into the local optimum in the process of iterative optimization . The simulation results show that the improved DV-Hop algorithm can effectively decrease the location errors and increase the precision of node positioning.

With the development of modern medicine, more and more methods can be used to diagnose cardiac diseases. At present, the conventional detection methods include X-ray, computed tomography (CT), magnetic resonance imaging (MRI), B-ultrasound, etc. However, the detection results are usually not intuitive enough, and it is difficult to support the sequential operation. We designed a multi-functional system based on the virtual reality (VR) equipment. We use CT and myocardial perfusion imaging (MPI) as data sources to build accurate cardiac models, and users can make operations such as rotation and scaling on these models. Experiment results have shown that the system allows users to observe cardiac tissue more intuitively, and realizes functions for the surgical program. This enables users to understand the cardiac condition more intuitively and accurately.

Aiming at the problems of static parameters and dynamic parameter testing of IGBT (Insulated Gate Bipolar Transistor), the error is large, the efficiency is low, and the test structure is poorly mixed. This paper proposes to use LabVIEWbased test system to measure the parameters. Using NI ELVIS as the measuring instrument platform, the ADC0809 single-chip microcomputer and the hardware circuit corresponding to the series voltage equalization are used as the execution process of the measurement process, making the measurement data more precise and stable. The stability and function of the IGBT are evaluated by measuring the saturation voltage drop, the off current and the switching off time as the measurement parameters.

Orientation field (OF) estimation is an important procedure in fingerprint image preprocessing. As for the hard problem that traditional methods cannot estimate the OF on incomplete fingerprint image accurately and the subsequent recognition will be influenced unavoidably, we propose an algorithm for the OF estimation which combines together the fidelity term of the local information from incomplete fingerprint image and a total variation (TV) regularization term. The local information involves the OFs evaluated by the traditional gradient-based method and the zero-pole model-based method. The experimental results demonstrate that proposed algorithm is effective in reconstructing the OF of incomplete fingerprint image.

Because low illumination color image has the features of low brightness, poor contrast and dark color, and the enhancement effect of traditional image enhancement algorithm is very limited. A low illumination image enhancement algorithm based on fuzzy set theory is proposed, by transformed the RGB image into HSV space, and the brightness component V of the image is used to enhance the image in fuzzy plane. The experimental results show that this method is better than the traditional enhancement according to fuzzy set and the operation efficiency is higher, which can realize the clearness processing of low illumination image effectively.

In the current investigation, a surface elastic-based three-dimensional (3D) nonlinear formulation is provided to explore the thermal postbuckling characteristics of porous composite nanoplates made of a functionally graded material (FGM) having a central cutout with different shapes. The surface stress factors are taken into the formulation by choosing the Gurtin-Murdoch theory of elasticity within the framework of a hybrid-type quasi-3D higher-order plate theory. With the aid of the isogeometric solving process using non-uniform rational B-splines as the basis functions, higher-order approximation with a precise geometric modelling of the structure is achieved. In the context of a refined power-law function together with the Touloukian scheme, the porosity-dependent as well as temperature-dependent material properties are achieved. It is portrayed that for a higher value of the material gradient index, the role of surface stress type of size dependency in the thermal postbuckling of porous FGM nanoplates becomes more important. Furthermore, it is deduced that by going to deeper part of the postbuckling regime which results in a higher value of the maximum deflection, the increment in the associated temperature rise caused by the surface stress size effect reduces. Also, it is found that by considering a higher value of the maximum deflection and moving to deeper region of the postbuckling domain, the existence of a central cutout leads to change the trend of the thermal postbuckling equilibrium path especially for a bigger central cutout.

Most rumors in social networks are extremely harmful and have a significant negative impact on social welfare. Therefore, exploring the laws of rumor propagation has been one of the hot topics in current researches. Most traditional rumor spreading models are based on infectious disease transmission models, such as SIR. Since the influence of individual differences and the network structure on rumor spreading are not considered, the rumor propagation process in complex networks can only be described in a coarse-grained manner. In this paper, we consider the role of different users in rumor propagation. Based on the degree of different nodes in the network, we design a new state transition function for each node and proposed a new rumor propagation ILSR model. Firstly, we analyze the model, calculate the equilibrium point and the basic reproductive number to prove the rationality of the model. Then experiments are performed in WS networks, BA scale-free networks and a real Facebook network to investigate the relationship between various nodes with time and the impact of network structure on rumor propagation, and the experimental results show the correctness and effectiveness of the model. It provides a reference for exploring the propagation law of rumors in complex networks and guiding and controlling the propagation of rumors.

Adaptor proteins are involved in the assembly of various intracellular complexes and the regulation of cellular functions. Membrane-associated guanylate kinase inverted 2 (MAGI2), also known as synaptic scaffolding molecule (S-SCAM), plays a critical role in signal transduction by assembling and anchoring its ligands. However, the role of MAGI2 in mediating apoptosis remains largely unknown. In the present study, BEL-7404 human hepatocellular carcinoma cells were transfected with a plasmid containing myc-MAGI2 or an empty plasmid and cell viability was then determined using the Cell Counting kit-8. Apoptosis was also detected using an Annexin V apoptosis assay. The cells were then treated with various doses of staurosporine (STS) for different periods of time. The overexpression of myc-MAGI2 was found to sensitize the BEL-7404 cells to apoptosis in response to STS in a time- and dose-dependent manner. Our results demonstrated that MAGI2 enhanced STS-induced apoptosis by increasing the protein expression of cytoplasmic phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and decreasing its protein degradation. The apoptotic sensitivity of the cells caused by the overexpression of myc-MAGI2 was reversed by the silencing of PTEN expression by PTEN siRNA, thus revealing a momentous role of PTEN in the enhancement of the sensitivity of cancer cells to STS-induced apoptosis by MAGI2. Finally, we observed that the MAGI-PTEN complex triggered by MAGI2 overexpression reduced the phosphorylation levels of AKT. These results suggest that MAGI2 overexpression enhances the sensitivity of cancer cells harboring ectopic PTEN to STS-induced apoptosis.

Dimerization among the EGFR family of tyrosine kinase receptors leads to allosteric activation of the kinase domains of the partners. Unlike other members in the family, the kinase domain of HER3 lacks key amino acid residues for catalytic activity. As a result, HER3 is suggested to serve as an allosteric activator of other EGFR family members which include EGFR, HER2 and HER4. To study the role of intracellular domains in HER3 dimerization and activation of downstream signaling pathways, we constructed HER3/HER2 chimeric receptors by replacing the HER3 kinase domain (HER3-2-3) or both the kinase domain and the C-terminal tail (HER3-2-2) with the HER2 counterparts and expressed the chimeric receptors in Chinese hamster ovary (CHO) cells. While over expression of the intact human HER3 transformed CHO cells with oncogenic properties such as AKT/ERK activation and increased proliferation and migration, CHO cells expressing the HER3-2-3 chimeric receptor showed significantly reduced HER3/HER2 dimerization and decreased phosphorylation of both AKT and ERK1/2 in the presence of neuregulin-1 (NRG-1). In contrast, CHO cells expressing the HER3-2-2 chimeric receptor resulted in a total loss of downstream AKT activation in response to NRG-1, but maintained partial activation of ERK1/2. The results demonstrate that the intracellular domains play a crucial role in HER3’s function as an allosteric activator and its role in downstream signaling.

Epidermal growth factor receptor variant III (EGFRvIII), the most common EGFR mutation, is associated with cell migration of glioblastoma multiforme (GBM) cases; however, the mechanism has not been elucidated. In this study, we found that the EGFRvIII-promoted glioma cell migration was closely linked to high levels of tyrosine phosphorylation in focal adhesion kinase (FAK) Y397. We also demonstrated that EGFRvIII formed a complex with FAK, resulting in enhanced tyrosine phosphorylation levels of FAK Y397 and EGFR Y1068. After knockdown of FAK expression via anti-FAK shRNA, the U87ΔEGFR cell migration was significantly inhibited, accompanying with the reduced phosphorylation levels of extracellular signal-regulated kinase (ERK1/2). Furthermore, the role of ERK1/2 in FAK-regulated cell migration was confirmed. Taken together, our results suggest that FAK and its downstream molecule ERK were involved in EGFRvIII-promoted glioma cell migration in U87ΔEGFR cells.

DNA methyltransferases (DNMTs) are essential for maintenance of aberrant methylation in cancer cells and play important roles in the development of cancers. Unregulated activation of PI3K/Akt pathway is a prominent feature of many human cancers including human hepatocellular carcinoma (HCC). In present study, we found that DNMT3B mRNA and protein levels were decreased in a dose- and time-dependent manner in HCC cell lines with LY294002 treatment. However, we detected that LY294002 treatment did not induce increase of the degradation of DNMT3B protein using protein decay assay. Moreover we found that Akt induced alteration of the expression of DNMT3B in cells transfected with myristylated variants of Akt2 or cells transfected with small interfering RNA respectively. Based on DNMT3B promoter dual-luciferase reporter assay, we found PI3K pathway regulates DNMT3B expression at transcriptional level. And DNMT3B mRNA decay analysis suggested that down-regulation of DNMT3B by LY294002 is also post-transcriptional control. Furthermore, we demonstrated that LY294002 down-regulated HuR expression in a time-dependent manner in BEL-7404. In summary, we have, for the first time, demonstrate that PI3K/Akt pathway regulates the expression of DNMT3B at transcriptional and post-transcriptional levels, which is particularly important to understand the effects of PI3K/Akt and DNMT3B on hepatocarcinogenesis.

PTEN is a critical tumor suppressor gene mutated frequently in various human cancers. Previous studies have showed that PTEN mRNA expression is down-regulated by TGF-beta1 in various cell lines. In present study, we have found that TGF-beta1 down-regulates PTEN mRNA and protein expression in a dose- and time-dependent manner in hepatocarcinoma cell line SMMC-7721. Based on the PTEN promoter dual-luciferase report assay, we have found that PTEN transcription is not affected by TGF-beta1. By using transcriptional inhibitor actinomycin D (Act D), the turnover rate of PTEN transcripts appeared to be accelerated during TGF-beta1 stimulation, which indicated that down-regulation of PTEN by TGF-beta1 was post-transcriptional. What interested us was that transfection of PTEN coding sequence increased TGF-beta1-induced degradation of PTEN mRNA, suggesting that PTEN coding region was account for TGF-beta1-mediated down-regulation of PTEN. In addition, TGF-beta1 down-regulated PTEN expression was blocked by the TbetaIR inhibitor SB431542 and the p38 inhibitor SB203580, suggesting Smad and p38 MAPK signal pathways played crucial roles in PTEN down-regulation via TGF-beta1 stimulation. In this study, we also found TGF-beta1 accelerated down-regulation of PTEN through the ubiquitin-proteasome pathway. Collectively, our data clearly demonstrated that TGF-beta1-mediated down-regulation of PTEN was post-transcriptional and post-translational, depending on its coding sequence, Smad and p38-MAPK signal pathways were involved in this down-regulation.

DNA methylation, which affects gene expression and chromatin stability, is catalyzed by DNA methyltransferases (DNMTs) of which DNMT1 possesses most abundant activity. PI3K/PKB pathway is an important pathway involved in cell proliferation, viability, and metabolism and often disrupted in cancer. Here we investigated the impact of PKB on DNMT1 and DNA methylation. Positive correlation between PKB-Ser473-phosphorylation and DNMT1 protein level in 17 human cell lines (p

MAGI-2, a multidomain scaffolding protein, contains nine potential protein-protein interaction modules, including a GuK domain, two WW domains and six PDZ domains. In this study, we examined eight human hepatocarcinoma cell lines (HHCCs) and found that MAGI-2 was expressed only in 7721 cells. After 7721, 7404 and 97H cells were transfected with myc-MAGI-2 plasmid, their migration and proliferation was significantly inhibited, which was associated with downregulation of p-FAK and p-Akt. It is known that p-FAK is a substrate of PTEN and p-Akt can be regulated by PTEN via PIP(3). We demonstrated that PTEN was upregulated after myc-MAGI-2 transfection, which was due to the enhancement of PTEN protein stability rather than mRNA levels. Furthermore, MAGI-2-induced inhibition of cell migration and proliferation was attenuated in 7721 cells with PTEN silence or in PTEN-null cell line U87MG, and PTEN transfection could restore the effect of MAGI-2 in U87MG cells. Finally, the molecular association between PTEN and MAGI-2 was confirmed. Our results suggested that PTEN played a critical role in MAGI-2-induced inhibition of cell migration and proliferation in HHCCs.

In this study, an enzymatic inactive mutant of GnT-V (delta cGnT-V) was constructed and transfected in SMMC 7721 cell line. Integrin beta1 in delta cGnT-V transfectants (delta c-7721) showed attenuation of the number of beta1-6 GlcNAc branching, whereas those in wtGnT-V transfectants (wt-7721) presented a beta1-6 GlcNAc-rich pattern. High integrin beta1 expression was observed in wt-7721 compared with mock cells (7721 cell transfected with the vector pcDNA3), while transfection of delta cGnT-V decreased the integrin beta1 expression, despite of no significant changes on integrin beta1 mRNA level in these cell lines. Pulse-chase experiment showed that Integrin beta1 in delta c-7721 was prone to quick degradation and its half-life was less than 3 h, on the contrary, the alleviating degradation of beta1 subunit was observed in wt-7721 where the beta1 subunit half-life was about 16 h, meanwhile, the degradation rate of beta1 subunit in mock cells was in between, about 10 h. More effective in promoting cell migration toward fibronectin and invasion through Matrigel was observed in wt-7721 while this was almost suppressed in delta c-7721. Our results suggest that the addition of beta1-6 GlcNAc branching caused more fully glycosylated mature form on integrin beta1 and inhibited beta1 protein degradation. Glycosylation caused by GnT-V directs integrin beta1 stability and more delivery to plasma membrane, subsequently promotes Fn-based cell migration and invasion.

Previous studies have shown that all-trans retinoic acid (ATRA) suppresses growth of hepatocarcinoma cell in vitro. To understand the underlying mechanisms, we investigated the protein expression profiles by 2-DE in hepatocarcinoma cell line SMMC-7721 treated with ATRA. Our results reveal that six proteins were differently expressed in response to ATRA. Using MS and database searching, they were identified as profilin 1, phosphoglycerate kinase 1, RuvB-like 1, alpha-enolase, pyridoxal kinase and F-actin capping protein. We selected the up-regulated protein, profilin 1 (PFN1), for further studies. The PFN1 expression was increased in response to ATRA in a dose- and time-dependent manner. The PFN1 expression was reduced dramatically in four hepatoma cell lines compared to L02 cell line of non-tumor origin. The PFN1 expression was also examined in 4 cases of primary hepatocarcinoma tissues by Western blot and 30 cases by tissues microarray. It was found that the protein level of PFN1 was lower in hepatocarcinoma tissues compared to that in the adjacent tissues. Similar to ATRA, overexpression of PFN1 led to inhibition of cell proliferation and migration. Furthermore, RNAi-based PFN1 knockdown could rescue the inhibitory effect of ATRA on cell proliferation and migration. In conclusion, ATRA inhibited cell proliferation and migration through up-regulation of PFN1.

N-acetylglucosaminyltransferase V (GnT-V) has been reported to be positively associated with tumor progression, but its mechanism still remains unknown. In the present study, we found that GnT-V overexpression not only changed the glycosylation of receptor protein tyrosine phosphatase kappa (RPTPκ) but also decreased its protein level. Moreover, GnT-V overexpression decreased cell calcium-independent adhesion and increased the tyrosine phosphorylation level of β-catenin, in which RPTPκ played an important role. Since RPTPκ has an RXKR motif, which is a favored cleavage site for furin, we used furin inhibitor to further explore the effect of RPTPκ on the change of cell adhesion and β-catenin signaling induced by GnT-V. Our results showed that preventing RPTPκ cleavage rescued the above effects of GnT-V, suggesting that furin cleavage could be one of the factors for RPTPκ to regulate cell adhesion and β-catenin signaling in GnT-V overexpression cell lines. In addition, the increased tyrosine phosphorylation level of β-catenin was associated with the increased nuclear level of β-catenin and downstream signaling molecules such as c-myc and cyclin D1 that were associated with cell proliferation. Our results suggest that GnT-V could decrease human hepatoma SMMC-7721 cell adhesion and promote cell proliferation partially through RPTPκ. J. Cell. Biochem. 109: 113–123, 2010. © 2009 Wiley-Liss, Inc.

E-cadherin, a well-characterized cell-cell adhesion molecule, executes multifunction roles on cell behaviors. However, its effect on chemo-resistance remains controversial. In this study, we found that E-cadherin positive breast cell lines were less sensitive to staurosporine compared to E-cadherin negative ones. Next, we substantiated that the expression of E-cadherin in MDA-MB-435 cells could partly counteract the cytotoxic effect induced by staurosporine through a series of apoptosis assay. The resistance of E-cadherin over-expressing cells to staurosporine may due to the up-regulation of Bcl-2/Bax ratio. When E-cadherin interference plasmids were transfected into MCF-7 cells, Bcl-2 expression was down-regulated. Moreover, perturbation of E-cadherin function by blocking the cell-cell contact resulted in decreased cellular levels of Bcl-2 protein expression. All these results demonstrated the chemo-resistance function of E-cadherin in the condition of staurosporine treatment, therefore, might contribute effective therapeutic strategies in breast carcinoma.

Background Previous studies demonstrated the EGF-targeted phagemid particles carrying siRNA against Akt could be expressed efficiently in the presence of hydroxycamptothecin (HCPT). However, no significant cell growth inhibition was obtained. This study was to further investigate whether the EGF-targeted phagemid particles carrying siRNA would be a promising tool for anti-cancer siRNA delivery. Results We found that pSi4.1-siFAK phagemid particles could significantly inhibit the expression of focal adhesion kinase in the HCPT-treated cells. Moreover, we also observed that the particles could potently suppress cell growth and cell invasion. Conclusion These results indicated that EGF-targeted phagemid particles might be a promising tool for anti-cancer siRNA delivery in the presence of HCPT.

Evidence has been emerging to suggest that integrin could induce growth inhibition in some cell types. Some of the molecular mechanisms underlying growth arrest have been elucidated. We reported here that overexpression of integrin beta1 imposed a growth inhibitory effect on the hepatocellular carcinoma cell line SMMC-7721, and this phenomenon was mainly attributed to the cyclin-dependent kinase inhibitor p21(CIP1). Furthermore, our findings suggested that transcription activity of the p21(CIP1) gene could be upregulated in the integrin beta1-overexpressing cells, and possibly controlled by the cis-elements in the core region of the p21(CIP1) promoter.