Signaling Transduction Network Mediated by Tumor Suppressor/Susceptibility Genes in NPC

Nasopharyngeal carcinoma (NPC) is a polygenetic disease. SPLUNC1, UBAP1, BRD7, NAG7, NOR1, NGX6 and LTF genes were found to be tumor suppressor/susceptibility genes in different stages of NPC. SPLUNC1, an early warning molecular diagnosis marker, inhibits the bacteria clone formation, and is an innated immune molecule. SPLUNC1 can negatively regulate the ERK/MAPK signaling transduction pathway to inhibit NPC cell proliferation and induce apoptosis. BRD7, a transcript regulation factor, interacts with BRD2, and promotes apoptosis induced by BRD2. Its promoter is regulated by c-Myc and SP1. BRD7 inhibits NPC cell cycle progression, preventing passage through G0/G1 by suppressing ras/MEK/ERK, Rb/E2F and Wnt signaling pathways. Abnormal activation of BRD7 is crucial to cell cycle turbulence in NPC. NGX6, a metastasis-associated protein, can negative-regulate the EGF/Ras/MAPK signaling transduction pathway, and interacts with ezrin protein to inhibit NPC cell invasion and metastasis. LTF, also a metastasis-associated protein, can negatively regulate MAPK signal transduction pathways, such as JNK2 and ERK, to inhibit NPC cell proliferation and growth. Taken together, it was found that these tumor suppressor/susceptibility genes can regulate key molecules involved in cell signal pathways such as ras/MEK/ERK, Rb/E2F and EGFR ras/MEK/MAPK, and can regulate the expression of some adhesion molecules such as ezrin, nm23 and α-catenin. According to functional genomics and signaling transduction pathways, we have described a signaling cross-talk network between the tumor suppressor/susceptibility genes involved in NPC. These tumor suppressor/susceptibility genes may be potential treatment targets for NPC in the future

Assessment of spatial coupling coordination in the Three Gorges reservoir area- Taking Badong County as an example

The special geographical location leads to the mutual restriction of urban spatial natural resources, material space and economy and society in the Three Gorges reservoir area, which threatens the spatial security of the towns. Based on the characteristics of multidimensional coupling between systems, this study uses Badong County as an example to evaluate the trend of coupling coordination between natural resources-material space-economic society and society by using the coupling coordination model. The results show that although the coupling degree between systems in Badong County is as high as 0.9546 and the degree of interaction is very strong, the degree of coupling coordination is only a moderate imbalance development type. Therefore, it is an urgent problem to improve the level of coupling and coordination between systems and ensure the safety of urban space

Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment.

Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In addition, ANKDD1A decreases the half-life of HIF1α by upregulating FIH1, decreases glucose uptake and lactate production, inhibits glioblastoma multiforme (GBM) autophagy, and induces apoptosis in GBM cells under hypoxia. Moreover, ANKDD1A is highly frequently methylated in GBM. The tumor-specific methylation of ANKDD1A indicates that it could be used as a potential epigenetic biomarker as well as a possible therapeutic target

NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). In this study, we explored the role of DNA methylation in regulation of NGX6 transcription.</p> <p>Methods</p> <p>In the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation.</p> <p>Results</p> <p>The sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P < 0.05). An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the NGX6 promoter was associated with colorectal cancer patients age (P < 0.05). Moreover, a trend was shown toward metastasis status and primary site in colorectal carcinomas with NGX6 promoter methylation (p = 0.056 and P = 0.067, respectively). In addition, 5-Aza-dC could induce NGX6 mRNA expression and NGX6 promoter demethylation in HT-29 cells.</p> <p>Conclusions</p> <p>Down-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.</p

Promoter Hypermethylation-mediated Inactivation of LRRC4 in Gliomas

<p>Abstract</p> <p>Background</p> <p>Leucine-rich repeat C4 protein (<it>LRRC4</it>) is a new member of the leucine-rich repeat (LRR) superfamily. It is not only a brain-specific gene but also a novel candidate for tumor suppression. <it>LRRC4 </it>inactivation is commonly found in glioma cell lines and primary glioma biopsies. However, little is known about the mechanism controlling <it>LRRC4 </it>expression. In a previous study, we did not find any genetic alteration in <it>LRRC4 </it>in primary glioma, which led us to explore an alternative mechanism underlying this phenomenon.</p> <p>Methods</p> <p>In the present paper, we cloned the <it>LRRC4 </it>promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the <it>LRRC4 </it>promoter region in glioma cell lines and primary gliomas was examined by methylation-specific PCR and bisulfite DNA sequencing. In order to demonstrate a functional association between <it>LRRC4 </it>promoter methylation and its gene inactivation, we performed DNA demethylation analysis with two human glioma cell lines using methylation-specific PCR and RT-PCR.</p> <p>Results</p> <p>The sequence spanning positions -835 to -293 relative to the translation start site was identified as the LRRC4 promoter; this sequence is a TATA- and CAAT- less, high GC content region. It was found that <it>LRRC4 </it>promoter activity is strongly suppressed after treatment with SssI methylase in vitro. Furthermore, LRRC4 promoter methylation was observed by methylation-specific PCR in two glioma cell lines and all 30 primary glioma specimens, but not in normal brain tissue. Bisulfite DNA sequencing showed that most of the CpG sites were located around the <it>LRRC4 </it>promoter methylated in glioma cells and tissues, but not in normal brain tissue. In addition, the methylase inhibitor 5-Aza-2'-deoxycytidine could induce <it>LRRC4 </it>mRNA expression and <it>LRRC4 </it>promoter partial demethylation in SF126 and SF767 glioma cells.</p> <p>Conclusion</p> <p>Methylation-mediated inactivation of <it>LRRC4 </it>is a frequent and glioma-specific event, and it may be a potential biomarker for diagnosis or prognosis, or serve as a therapeutic target.</p

Multi-branch Joint Representation Learning Based on Information Fusion Strategy for Cross-view Geo-localization

Cross-view geo-localization refers to recognizing images of the same geographic target obtained from different platforms (such as drone-view, satellite-view, and ground-view). However, cross-view geo-localization is challenging as image capture using different platforms coupled with extreme viewpoint variations can cause significant changes to the visual image content. Existing methods mainly focus on mining the fine-grained features or the contextual information in neighboring areas, but ignore the complete information of the entire image and the association of contextual information of adjacent regions. Therefore, a multibranch joint representation learning network model based on information fusion strategies (IFSs) is proposed to solve this cross-view geo-localization problem. First, we obtained feature information from the image through global information fusion (GIF) branch and local information fusion (LIF) branch to help the network learn the discernable information in the different images. In addition, a local-guided-GIF (LGGIF) branch is introduced to make local information assist global features to enhance the learning of potential information in the images. Second, we introduced different IFSs in each branch to increase the extraction of contextual information through expanding the global receptive field, thus improving the performance of the model. Finally, a series of experiments is carried out on four prevailing benchmark datasets, namely University-1652, SUES-200, CVUAS, and CVACT datasets. The quantitative comparisons from the experiments clearly indicate that the proposed network framework has great performance. For example, compared with some state-of-the-art methods, the quantitative improvements of the R@1 and AP on the University-1652 datasets are 1.91%, 2.18%, and 1.55%, 2.99% in both tasks, respectively

Utility of EST-derived SSR in cultivated peanut (Arachis hypogaea L.) and Arachis wild species

<p>Abstract</p> <p>Background</p> <p>Lack of sufficient molecular markers hinders current genetic research in peanuts (<it>Arachis hypogaea </it>L.). It is necessary to develop more molecular markers for potential use in peanut genetic research. With the development of peanut EST projects, a vast amount of available EST sequence data has been generated. These data offered an opportunity to identify SSR in ESTs by data mining.</p> <p>Results</p> <p>In this study, we investigated 24,238 ESTs for the identification and development of SSR markers. In total, 881 SSRs were identified from 780 SSR-containing unique ESTs. On an average, one SSR was found per 7.3 kb of EST sequence with tri-nucleotide motifs (63.9%) being the most abundant followed by di- (32.7%), tetra- (1.7%), hexa- (1.0%) and penta-nucleotide (0.7%) repeat types. The top six motifs included AG/TC (27.7%), AAG/TTC (17.4%), AAT/TTA (11.9%), ACC/TGG (7.72%), ACT/TGA (7.26%) and AT/TA (6.3%). Based on the 780 SSR-containing ESTs, a total of 290 primer pairs were successfully designed and used for validation of the amplification and assessment of the polymorphism among 22 genotypes of cultivated peanuts and 16 accessions of wild species. The results showed that 251 primer pairs yielded amplification products, of which 26 and 221 primer pairs exhibited polymorphism among the cultivated and wild species examined, respectively. Two to four alleles were found in cultivated peanuts, while 3–8 alleles presented in wild species. The apparent broad polymorphism was further confirmed by cloning and sequencing of amplified alleles. Sequence analysis of selected amplified alleles revealed that allelic diversity could be attributed mainly to differences in repeat type and length in the microsatellite regions. In addition, a few single base mutations were observed in the microsatellite flanking regions.</p> <p>Conclusion</p> <p>This study gives an insight into the frequency, type and distribution of peanut EST-SSRs and demonstrates successful development of EST-SSR markers in cultivated peanut. These EST-SSR markers could enrich the current resource of molecular markers for the peanut community and would be useful for qualitative and quantitative trait mapping, marker-assisted selection, and genetic diversity studies in cultivated peanut as well as related <it>Arachis </it>species. All of the 251 working primer pairs with names, motifs, repeat types, primer sequences, and alleles tested in cultivated and wild species are listed in Additional File <supplr sid="S1">1</supplr>.</p> <suppl id="S1"> <title> <p>Additional File 1</p> </title> <text> <p><b>List of EST-SSR primers developed from cultivated peanut ESTs</b>. The file contains a table that lists primer names, repeat motifs, primer sequences, allele number and product length for the newly developed EST-SSR markers.</p> </text> <file name="1471-2229-9-35-S1.xls"> <p>Click here for file</p> </file> </suppl