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

Application of atomic force microscopy in cancer research

Atomic force microscopy (AFM) allows for nanometer-scale investigation of cells and molecules. Recent advances have enabled its application in cancer research and diagnosis. The physicochemical properties of live cells undergo changes when their physiological conditions are altered. These physicochemical properties can therefore reflect complex physiological processes occurring in cells. When cells are in the process of carcinogenesis and stimulated by external stimuli, their morphology, elasticity, and adhesion properties may change. AFM can perform surface imaging and ultrastructural observation of live cells with atomic resolution under near-physiological conditions, collecting force spectroscopy information which allows for the study of the mechanical properties of cells. For this reason, AFM has potential to be used as a tool for high resolution research into the ultrastructure and mechanical properties of tumor cells. This review describes the working principle, working mode, and technical points of atomic force microscopy, and reviews the applications and prospects of atomic force microscopy in cancer research

Understanding the Adoption of Smart Community Services: Perceived Usefulness, Enjoyment, and Affective Community Commitment

Smart community is an emerging form of community that provides various convenient services (smart community services (SCS)) through smart community platform to community residents. However, in practice, residents have limited SCS acceptance, which deserves to be further investigated in the literature. This study investigates the SCS adoption of residents by integrating technological belief factors (perceived usefulness and enjoyment), and social influence factor (affective community commitment). A survey of 191 residents identifies perceived usefulness, perceived enjoyment, and affective community commitment as important determinants of SCS adoption. Affective community commitment weakens the effect of perceived enjoyment yet strengthen the effect of perceived usefulness on SCS adoption. Our study fills the research gap on smart community as well as enriches the IT acceptance literature. This study also offers practical recommendations that can aid practitioners in conducting smart community programs

Fast Nearest Neighbor Machine Translation

Though nearest neighbor Machine Translation ($k$NN-MT) \citep{khandelwal2020nearest} has proved to introduce significant performance boosts over standard neural MT systems, it is prohibitively slow since it uses the entire reference corpus as the datastore for the nearest neighbor search. This means each step for each beam in the beam search has to search over the entire reference corpus. $k$NN-MT is thus two-orders slower than vanilla MT models, making it hard to be applied to real-world applications, especially online services. In this work, we propose Fast $k$NN-MT to address this issue. Fast $k$NN-MT constructs a significantly smaller datastore for the nearest neighbor search: for each word in a source sentence, Fast $k$NN-MT first selects its nearest token-level neighbors, which is limited to tokens that are the same as the query token. Then at each decoding step, in contrast to using the entire corpus as the datastore, the search space is limited to target tokens corresponding to the previously selected reference source tokens. This strategy avoids search through the whole datastore for nearest neighbors and drastically improves decoding efficiency. Without loss of performance, Fast $k$NN-MT is two-orders faster than $k$NN-MT, and is only two times slower than the standard NMT model. Fast $k$NN-MT enables the practical use of $k$NN-MT systems in real-world MT applications. The code is available at \url{https://github.com/ShannonAI/fast-knn-nmt}Comment: To appear at ACL 2022 Finding

Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL

Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P<0.05 compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P<0.05). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P<0.05). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue

Transcriptional regulation of BRD7 expression by Sp1 and c-Myc

<p>Abstract</p> <p>Background</p> <p>Bromodomain is an evolutionally conserved domain that is found in proteins strongly implicated in signal-dependent transcriptional regulation. Genetic alterations of bromodomain genes contributed to the development of many human cancers and other disorders. BRD7 is a recently identified bromodomain gene. It plays a critical role in cellular growth, cell cycle progression, and signal-dependent gene expression. Previous studies showed that BRD7 gene exhibited much higher-level of mRNA expression in normal nasopharyngeal epithelia than in nasopharyngeal carcinoma (NPC) biopsies and cell lines. However, little is known about its transcriptional regulation. In this study, we explored the transcriptional regulation of BRD7 gene.</p> <p>Method</p> <p>Potential binding sites of transcription factors within the promoter region of BRD7 gene were predicted with MatInspector Professional <url>http://genomatix.de/cgi-bin/matinspector_prof/mat_fam.pl</url>. Mutation construct methods and luciferase assays were performed to define the minimal promoter of BRD7 gene. RT-PCR and western blot assays were used to detect the endogenous expression of transcription factor Sp1, c-Myc and E2F6 in all cell lines used in this study. Electrophoretic mobility shift assays (EMSA) and Chromatin immunoprecipitation (ChIP) were used to detect the direct transcription factors that are responsible for the promoter activity of BRD7 gene. DNA vector-based siRNA technology and cell transfection methods were employed to establish clone pools that stably expresses SiRNA against c-Myc expression in nasopharyngeal carcinoma 5-8F cells. Real-time PCR was used to detect mRNA expression of BRD7 gene in 5-8F/Si-c-Myc cells.</p> <p>Results</p> <p>We defined the minimal promoter of BRD7 gene in a 55-bp region (from -266 to -212bp), and identified that its promoter activity is inversely related to c-Myc expression. Sp1 binds to the Sp1/Myc-Max overlapping site of BRD7 minimal promoter, and slightly positively regulate its promoter activity. c-Myc binds to this Sp1/Myc-Max overlapping site as well, and negatively regulates the promoter activity and endogenous mRNA expression of BRD7 gene. Knock-down of c-Myc increases the promoter activity and mRNA level of BRD7 gene. The luciferase activity of the mutated promoter constructs showed that Sp1/Myc-Max overlapping site is a positive regulation element of BRD7 promoter.</p> <p>Conclusion</p> <p>These studies provide for the first time the evidence that c-Myc is indeed a negative regulator of BRD7 gene. These findings will help to further understand and uncover the bio-functions of BRD7 gene involved in the pathogenesis of NPC.</p