In cellular networks, proximity users may communicate directly without going through the base station, which is called Device-to-device (D2D) communications and it can improve spectral efficiency. ...However, D2D communications may generate interference to the existing cellular networks if not designed properly. In this paper, we study a resource allocation problem to maximize the overall network throughput while guaranteeing the quality-of-service (QoS) requirements for both D2D users and regular cellular users (CUs). A three-step scheme is proposed. It first performs admission control and then allocates powers for each admissible D2D pair and its potential CU partners. Next, a maximum weight bipartite matching based scheme is developed to select a suitable CU partner for each admissible D2D pair to maximize the overall network throughput. Numerical results show that the proposed scheme can significantly improve the performance of the hybrid system in terms of D2D access rate and the overall network throughput. The performance of D2D communications depends on D2D user locations, cell radius, the numbers of active CUs and D2D pairs, and the maximum power constraint for the D2D pairs.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
Cancer stem cells are undifferentiated cancer cells that have self‐renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in ...regulating gene expression during carcinogenesis. Here, we investigated the role of miR‐7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence‐activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real‐time polymerase chain reaction (PCR) revealed that the miR‐7‐5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine‐deprived medium. The downregulation of miR‐7‐5p results from the increased DNA methylation in the promoter region using the methylation‐specific PCR. Overexpression of miR‐7‐5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR‐7‐5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR‐7‐5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.
Background
Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of ...autophagy and CDDP resistance of gastric cancer cells is still not clear.
Materials and methods
Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay.
Results
Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo.
Conclusion
METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
Background/Aims
Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here, we prepare an active targeting drug carrier of low immunogenicity and ...toxicity for targeted therapy.
Methods
Immature dendritic cells (imDCs) from BALB/c mice were used as donor cells of exosomes (Exos) that were transfected with the plasmids expressing fusion proteins of a tumor-targeting peptide known as internalizing RGD (iRGD) to construct a type of tumor-targeting iRGD-Exos and observe the interaction between these iRGD-Exos. Also, recombinant methioninase (rMETase) was loaded into the iRGD-Exos by electroporation to construct iRGD-Exos-rMETase and to assess the tumor-targeting function of the iRGD-Exos-rMETase. Finally, 30 BALB/c were randomly divided into five groups (
n
= 6), to observe tumor growth in vivo.
Results
The iRGD-Exos-rMETase was 99.58 nm in diameter and presented a unique “goblet” structure under transmission electron microscopy (TEM), with the encapsulation efficiency (EE) of 19.05%. iRGD-Exos-rMETase group has the strongest tumor suppressive effect. Compared to the iRGD-Exos-rMETase group, rMETase group and the blank-Exos-rMETase group were less effective, while the PBS group and the iRGD-Exos group showed no inhibitory effect on tumor growth. After treatment, the iRGD-Exos-rMETase group had gastric tumors significantly smaller and lighter than the other groups (
P
< 0.05).
Conclusion
The iRGD-Exos-rMETase is an effective antitumor therapy that delivers rMETase to tumor tissue using the iRGD-Exos. With its favorable inhibitory effect and tumor-targeting function, the iRGD-Exos-rMETase shows excellent potential value and exciting prospects in clinical applications.
In device-to-device (D2D) communications, channel state information (CSI) is exploited to manage the interference between D2D users and regular cellular users (CUs) and improve system performance. ...However, obtaining the accurate CSI is usually difficult and causes high overhead, particularly when the links are not connected to the base station (BS), such as the links between regular CUs and D2D receivers (CU-D links). In this paper, we investigate the signaling overhead and performance tradeoff in D2D communications with channel uncertainty. To limit interference to regular CUs, we only allow the resource of a CU to be reused by, at most, one D2D pair. We also assume that only partial CSI of the CU-D links is available at the BS and develop two different strategies to deal with the channel uncertainty, namely, probabilistic and partial feedback schemes. We first derive a probability-based resource-allocation scheme by utilizing channel statistical characteristics to maximize the overall throughput of the CUs and admissible D2D pairs while guaranteeing their quality of service (QoS) in terms of signal-to-interference-plus-noise ratio (SINR) and outage probability, respectively. Then, we propose an efficient feedback scheme to reduce the overhead of CSI feedback while providing near-optimal performance. In addition, we propose a combined scheme to take advantages of both probabilistic and partial feedback schemes. It is shown by simulation that there exists an optimal threshold of the outage probability for probabilistic scheme while the partial feedback scheme is robust to the channel models. Furthermore, the combined scheme outperforms the probabilistic and the partial feedback schemes in terms of overall throughput.
In this paper, we study resource allocation for full-duplex communications in an orthogonal frequency division multiple access femtocell network. We aim to maximize the throughput of the femtocell ...while avoiding severe inter-tier interference to the macrocell via joint sub-channel assignment and power allocation. To be more practical, we take channel estimation error into account and use the robust optimization theory to model the uncertainty in interference channels. By using the Lagrangian dual method, we decompose the original optimization problem into a primal problem and a dual problem. We adopt the concave-convex procedure to transform the non-convex primal problem into a tractable form through sequential convex approximations and then utilize the sub-gradient method to solve the dual problem. Simulation results show the effectiveness of the proposed algorithm and demonstrate the impact of channel uncertainty on the system performance.
The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by ...methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for
experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for
experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation
compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.
Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin‐like growth factor (IGF2) and hepatocyte growth ...factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high‐grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co‐injection model, we observed that FF co‐injection induced tumorigenesis of STIC‐mimicking cells, FE25. Co‐injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co‐injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring‐independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine‐protein kinase Met (cMET)/mitogen‐activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF‐IGF2 could mediate clonogenicity and stemness activities via the IGF‐1R/AKT/mammalian target of rapamycin and IGF‐1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF‐sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.
Herein, we report the ultrasensitive DNA detection through designing an elegant nanopore biosensor as the first case to realize the reversal of current rectification direction for sensing. Attributed ...to the unique asymmetric structure, the glass conical nanopore exhibits the sensitive response to the surface charge, which can be facilely monitored by ion current rectification curves. In our design, an enzymatic cleavage reaction was employed to alter the surface charge of the nanopore for DNA sensing. The measured ion current rectification was strongly responsive to DNA concentrations, even reaching to the reversed status from the negative ratio (−6.5) to the positive ratio (+16.1). The detectable concentration for DNA was as low as 0.1 fM. This is an ultrasensitive and label‐free DNA sensing approach, based on the rectification direction‐reversed amplification in a single glass conical nanopore.
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