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Gao, J.

Publications and source records attributed to Gao, J..

At least 253 records · Page 14Linked to original sources
bioRxiv2020

Susceptibility of tree shrew to SARS-CoV-2 infection

Since SARS-CoV-2 became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and COVID-19 were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39{degrees} C) particular in female animals during infection. Low levels of virus shedding and replication in tissues occurred in all three age groups, each of which showed his own characteristics. Histopathological examine revealed that pulmonary abnormalities were mild but the main changes although slight lesions were also observed in other tissues. In summary, tree shrew is not susceptible to SARS-CoV-2 infection and may not be a suitable animal for COVID-19 related researches.

microbiology↗
bioRxiv2020

Gene interfered-ferroptosis therapy of cancer

Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we developed a novel therapy named as gene interfered-ferroptosis therapy (GIFT) by combining iron nanoparticles and cancer-specific gene interference. Using a promoter consisted of a NF-{kappa}B decoy and a minimal promoter (DMP), we knocked down the expression of two iron metabolism-related genes (FPN and Lcn2) selectively in cancer cells. At the same time, we treated cells with Fe3O4 nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells representing various hematological and solid tumors. However, the same treatment had no effect on normal cells. By using AAV and PEI-coated Fe3O4 nanoparticles as gene vectors, we found that the tumor growth in mice could be also significantly inhibited by the intravenously injected GIFT reagents. By detecting ROS, iron content and gene expression, we confirmed that the mechanism underlying the therapy is gene inference-enhanced ferroptosis.

cancer biology↗
bioRxiv2020

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence SummaryM. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.

microbiology↗
bioRxiv2020

SARS-CoV-2 neutralizing serum antibodies in cats: a serological investigation

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. Previous studies suggested cat could be a potential susceptible animal of SARS-CoV-2. Here, we investigated the infection of SARS-CoV-2 in cats by detecting specific serum antibodies. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among the positive samples, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between the SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). Our data demonstrates that SARS-CoV-2 has infected cat population in Wuhan during the outbreak.

microbiology↗
bioRxiv2020

Glycyrrhizic acid improves cognitive levels of aging mice by regulating T/B cell proliferation

Dear Editor,Licorice is the root of Glycyrrhiza glabra L. (Leguminosae), which grows in various warm climates such as the Middle East, Asia, and Southern Europe. It is one of the oldest known medicinal herbs and is referred to as "the father of herbal medicine." Glycyrrhizic acid (GA) (Fig. 1A), a triterpenoid saponin, is a major component of licorice. It has a variety of pharmacological activities such as anti-inflammatory, antioxidant, anticancer, neuroprotective, and immune effects, among others.[1]. Previous studies indicated that GA produces robust neuroprotection via the modulation of anti-apoptotic and pro-apoptotic factors, primarily through the ERK signaling pathway and its anti-inflammatory properties against high-mobility group box 1 phosphorylation and the suppression of inflammatory cytokine induction [2-4]. These results were based on pathological models. Although numerous pathways have been implicated in the neuroprotective effects of GA, the molecular mechanisms are not yet completely understood. In this study, we aimed to investigate the effects of GA in preventing age-related immune involution and cognitive disorders, the relationship between immune involution and cognition, and the underlying molecular mechanisms. O_FIG O_LINKSMALLFIG WIDTH=141 HEIGHT=200 SRC="FIGDIR/small/008821v1_fig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@5a123dorg.highwire.dtl.DTLVardef@163a085org.highwire.dtl.DTLVardef@1bfadb6org.highwire.dtl.DTLVardef@125b2ae_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Glycyrrhizic acid ameliorated cognitive declines in aged mice, improved CBF and increased T and B cell numbers. A. The chemical structure of glycyrrhizic acid (GA). B. Escape latencies from six consecutive daily tests. C. The first platform-finding latencies in the probe trial. D. The time spent in the target quadrant in the probe trial. E. The target platform crossing times in the probe trial. F. Images of CBF in C57BL/6 mice. G. Quantification of blood perfusion in the ipsilateral hemisphere. H. Bubble diagram showing GA treatment influence on hematopoietic cell lineage. I. Heatmap showing actively expressed genes related to T cells in the hematopoietic cell lineage of control and GA-treated C57BL/6 mice. J. Representative FACS plots showing CD3e+ T and CD45R/B220+ B cells in the spleens of C57BL mice; bar graphs showing the statistical analysis of T and B cells in the spleens of C57BL mice. K. Representative FACS plots showing CD3e+ T and CD45R/B220+ B cells in the blood of C57BL mice; Bar graphs showing the statistical results of T and B cell analyses in the blood of C57BL mice. GA (5mg/kg, once every other day); Data represent mean {+/-} SEM (n = 8 per group). *P < 0.05, **P < 0.01, ***P < 0.001 vs. Ctrl. C_FIG

animal behavior and cognition↗
bioRxiv2020

mrMLM v4.0: An R Platform for Multi-locus Genome-wide Association Studies

Previous studies reported that some important loci are missed in single-locus genome-wide association studies (GWAS), especially because of the large phenotypic error in field experiments. To solve this issue, multi-locus GWAS methods have been recommended. However, only a few software packages are available. Therefore, an R software mrMLM, which includes our six multi-locus methods, was developed. mrMLM includes three components: dataset input, parameter setting and result output. The fread function in data.table is used to quickly read datasets, especially big datasets, and the doParallel package is used to conduct parallel computation using multiple CPUs. In addition, the graphical user interface software mrMLM.GUI v4.0, built upon Shiny, is also available. To confirm the correctness of the above programs, the same simulation datasets as used in previous studies, along with three real datasets, were re-analyzed by all the methods in mrMLM v4.0 and three widely-used methods. The results confirmed the advantages of our multi-locus methods over the current methods. The conclusion is also consistent with those in a Research Topic in Frontiers in Plant Science. Although a less stringent significance threshold is adopted, the false positive rates are effectively controlled. mrMLM is publicly available at https://cran.r-project.org/web/packages/mrMLM/index.html or https://bigd.big.ac.cn/biocode/tools/BT007077 as an open-source software.

genetics↗
bioRxiv2020

CandiHap: a toolkit for haplotype analysis for sequence of samples and fast identification of candidate causal gene(s) in genome-wide association study

Genome-wide association study (GWAS) is widely used to identify genes involved in plants, animals and human complex traits. Generally, the identified SNP is not necessarily the causal variant, but it is rather in linkage disequilibrium (LD). One key challenge for GWAS results interpretation is to rapidly identify causal genes and provide profound evidence on how they affect the trait. Researches want to identify candidate causal variants from the most significant SNPs of GWAS in any species and on their local computer, while to complete these tasks are to be time-consuming, laborious and prone to errors and omission. To our knowledge, so far there is no tool available to solve the challenge for GWAS data very quickly. Based on the standard VCF (variant call format) format, CandiHap is developed to fast preselection candidate causal SNPs and gene(s) from GWAS by integrating LD result, SNP annotation, haplotype analysis and traits statistics of haplotypes. Investigators can specify genes or linkage regions based on GWAS results, linkage disequilibrium (LD), and predicted candidate causal gene(s). It supported Windows, Mac and Linux computers and servers in graphical interface and command line, and applied to any other plant, animal or bacteria species. The source code of CandiHap tool is freely available at https://github.com/xukaili/CandiHap

bioinformatics↗
bioRxiv2020

miR169 and PmRGL2 synergistically regulate NF-Y complex to active dormancy release in Japanese apricot (Prunus mume Sieb. et Zucc.)

Insufficient chilling requirements affect the floral bud quality and fruit yield in fruit crop production. Endodormancy is a process to meet the chilling requirement. To understand the mechanism of dormancy release in woody plants, we compared the miRNA database during the transition stage from endodormancy to dormancy release in Japanese apricot and found that the miR169 family showed significant differentially up-regulated expression during dormancy and down-regulated during dormancy release periods. The 5 RACE assay and RT-qPCR validated its target gene NUCLEAR FACTOR-Y subunit A (NF-YA) exhibited the opposite expression pattern. Further study showed that exogenous GA4 could inhibit the expression of PmRGL2 and promote the expression of NF-Y. Moreover, the interaction between NF-Y family and GA inhibitor PmRGL2 was verified by yeast-two-hybrid system and Bimolecular fluorescence complementarity (BiFC) experiment. These results suggested that synergistic regulation of NF-Y and PmRGL2 complex to active dormancy release induced by GA4. These will help to elucidate the functional and regulatory roles of miR169 and its target gene of the seasonal bud dormancy induced by GA4 in Japanese apricot woody plants and to provide new sights for the discovery of dormancy release mechanism.

molecular biology↗
bioRxiv2020

Agewise mapping of genomic oxidative DNA modification demonstrates oxidative-driven reprogramming of pro-longevity genes

The accumulation of unrepaired oxidatively damaged DNA can influence both the rate of ageing and life expectancy of an organism. Mapping oxidative DNA damage sites at whole-genome scale will help us to recognize the damage-prone sequence and genomic feature information, which is fundamental for ageing research. Here, we developed an algorithm to map the whole-genome oxidative DNA damage at single-base resolution using Single-Molecule Real-Time (SMRT) sequencing technology. We sequenced the genomic oxidative DNA damage landscape of C. elegans at different age periods to decipher the potential impact of genomic DNA oxidation on physiological ageing. We observed an age-specific pattern of oxidative modification in terms of motifs, chromosomal distribution, and genomic features. Integrating with RNA-Seq data, we demonstrated that oxidative modification in promoter regions was negatively associated with the expression of pro-longevity genes, denoting that oxidative modification in pro-longevity genes may exert epigenetic potential and thus affect lifespan determination. Together, our study opens up a new field for exploration of "oxigenetics," that focuses on the mechanisms of redox-mediated ageing. SummaryO_LIWe developed an algorithm to map the oxidative DNA damage at single-base resolution. C_LIO_LIOxidative DNA damage landscape in C. elegans illustrated an age-specific pattern in terms of motifs, chromosomal distribution, and genomic features. C_LIO_LIOxidative modification in older worms occurred higher frequency at the sex chromosome, with the preference for promoter and exon regions. C_LIO_LIOxidative modification in promoter regions of pro-longevity genes was negatively associated with their expression, suggesting the oxidative-driven transcript reprogramming of pro-longevity genes in physiological ageing. C_LI

genetics↗
bioRxiv2020

Differentiating the Roles of UL16, UL21 and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids

Previous studies from our laboratory established that pUL16 and pUL21 are required for efficient nuclear egress of herpes simplex type 2 (HSV-2) capsids. To better understand the role of these proteins in nuclear egress, we wished to establish whether nuclear egress complex (NEC) localization and/or function was altered in the absence of either pUL16 or pUL21. We used antiserum raised against HSV-2 NEC components pUL31 and pUL34 to examine NEC localization by immunofluorescence microscopy. NEC localization in cells infected with pUL16 deficient viruses was indistinguishable from that observed in cells infected with wild type viruses. By contrast, NEC localization was found to be aberrant in cells infected with pUL21 deficient virus and, instead, showed some similarity to the aberrant NEC localization pattern observed in cells infected with pUs3 deficient virus. These results indicated that pUL16 plays a role in nuclear egress that is distinct from that of pUL21 and pUs3. Higher resolution examination of nuclear envelope ultrastructure in cells infected with pUL21 deficient viruses by transmission electron microscopy showed different types of nuclear envelope perturbations, including some that were not observed in cells infected with pUs3 deficient virus. The formation of the nuclear envelope perturbations observed in pUL21 deficient virus infections was found to be dependent on a functional NEC, revealing a novel role for pUL21 in regulating NEC activity. The results of comparisons of nuclear envelope ultrastructure in cells infected with viruses lacking pUs3, pUL16 or both pUs3 and pUL16 were consistent with a role for pUL16 upstream of primary capsid envelopment and shed new light on how pUs3 functions in nuclear egress. Author summaryThe membrane deformation activity of the herpesvirus nuclear egress complex (NEC), allows viral capsids to transit from their site of assembly in the nucleus through both nuclear membranes into the cytoplasm. The timing, extent and directionality of NEC activity must be precisely controlled during viral infection, yet our knowledge of how NEC activity is controlled is incomplete. To determine how pUL16 and pUL21, two viral proteins required for nuclear egress of herpes simplex virus type 2 (HSV-2) capsids, function to promote nuclear egress, we examined how the lack of each protein impacted NEC localization. These analyses revealed a function of pUL16 in nuclear egress that is distinct from that of pUL21, uncovered a novel role for pUL21 in regulating NEC activity and shed new light on how a viral kinase, pUs3, regulates nuclear egress. Nuclear egress of viral capsids is a common feature of the replicative cycle of all herpesviruses. A complete understanding of all aspects of nuclear egress, including how viral NEC activity is controlled, may yield strategies to disrupt this process that could be applied to the development of herpes-specific antiviral drugs.

microbiology↗
bioRxiv2020

Tumor Neoantigenicity Assessment with CSiN Score Incorporates Clonality and Immunogenicity to Predict Immunotherapy Outcomes

Lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy. Tumor neoantigens are critical mediators of host immune response and immunotherapy treatment efficacy. Current studies of neoantigens almost entirely focus on total neoantigen load, which simplistically treats all neoantigens equally. Besides, neoantigen loads have been linked with treatment response and prognosis only in some studies, but not others. We developed a Cauchy-Schwarz index of Neoantigens (CSiN) score to characterize the degree of concentration of immunogenic neoantigens in truncal mutations. Unlike simple neoantigen loads, CSiN incorporates the effect of both clonality and MHC-binding affinity of neoantigens when characterizing patient neoantigen profiles. By exploiting the clinical responses in 501 treated patients (mostly by checkpoint inhibitors) and the overall survival of 1,978 baseline patients, we showed that CSiN scores predict treatment response to checkpoint inhibitors and prognosis in melanoma, lung cancer, and kidney cancer patients. CSiN substantially outperforms prior genetics-based prediction methods of responsiveness. Overall, our work fulfilled an important gap in current research involving neoantigens. One Sentence SummaryThe quality of tumor neoantigens predicts response to immunotherapy

bioinformatics↗
bioRxiv2019

To mock or not: a comprehensive comparison of mock IP and DNA input for ChIP-seq

Chromatin immunoprecipitation (IP) followed by sequencing (ChIP-seq) is the gold standard to detect genome-wide DNA-protein binding. The binding sites of transcription factors facilitate many biological studies. Of emerging concern is the abundance of spurious sites in ChIP-seq, which are mainly caused by uneven genomic sonication and nonspecific interactions between chromatin and antibody. A "mock" IP is designed to correct for both factors, whereas a DNA input control corrects only for uneven sonication. However, a mock IP is more susceptible to technical noise than a DNA input, and empirically, these two controls perform similarly for ChIP-seq. Therefore, DNA input is currently being used almost exclusively. With a large dataset, we demonstrate that using a DNA input control results in a definable set of spurious sites, and their abundance is tightly associated with the intrinsic properties of the ChIP-seq sample. For example, compared to human cell lines, samples such as human tissues and whole worm and fly have more accessible genomes, and thus have more spurious sites. The large and varying abundance of spurious sites may impede comparative studies across multiple samples. In contrast, using a mock IP as control substantially removes these spurious sites, resulting in high-quality binding sites and facilitating their comparability across samples. Although outperformed by mock IP, DNA input is still informative and has unique advantages. Therefore, we have developed a method to use both controls in combination to further improve binding site detection.

genomics↗
bioRxiv2019

Rapid, selective and single cell electrical detection of antibiotic resistant bacteria

The rapid increase in antibiotic resistant pathogenic bacteria has become a global threat, which besides the development of new drugs, requires rapid, cheap, scalable, and accurate diagnostics. Label free biosensors relying on electrochemical, mechanical, and mass based detection of whole bacterial cells have attempted to meet these requirements. However, the trade-off between selectivity and sensitivity of such sensors remains a key challenge. In particular, point-of-care diagnostics that are able to reduce and/or prevent unneeded antibiotic prescriptions require highly specific probes with sensitive and accurate transducers that can be miniaturized and multiplexed, and that are easy to operate and cheap. Towards achieving this goal, we present a number of advances in the use of graphene field effect transistors (G-FET) including the first use of peptide probes to electrically detect antibiotic resistant bacteria in a highly specific manner. In addition, we dramatically reduce the needed concentration for detection by employing dielectrophoresis for the first time in a G-FET, allowing us to monitor changes in the Dirac point due to individual bacterial cells. Specifically, we realized rapid binding of bacterial cells to a G-FET by electrical field guiding to the device to realize an overall 3 order of magnitude decrease in cell-concentration enabling a single-cell detection limit, and 9-fold reduction in needed time to 5 minutes. Utilizing our new biosensor and procedures, we demonstrate the first selective, electrical detection of the pathogenic bacterial species Staphylococcus aureus and antibiotic resistant Acinetobacter baumannii on a single platform.

microbiology↗
bioRxiv2019

A complex structure of arrestin-2 bound to a G protein-coupled receptor

Arrestins comprise a family of signal regulators of G-protein-coupled receptors (GPCRs), which include arrestins 1 to 4. While arrestins 1 and 4 are visual arrestins dedicated to rhodopsin, arrestins 2 and 3 (Arr2 and Arr3) are {beta}-arrestins known to regulate many nonvisual GPCRs. The dynamic and promiscuous coupling of Arr2 to nonvisual GPCRs has posed technical challenges to tackle the basis of arrestin binding to GPCRs. Here we report the structure of Arr2 in complex with neurotensin receptor 1 (NTSR1), which reveals an overall assembly that is strikingly different from the visual arrestin-rhodopsin complex by a 90{degrees} rotation of Arr2 relative to the receptor. In this new configuration, intracellular loop 3 (ICL3) and transmembrane helix 6 (TM6) of the receptor are oriented toward the N-terminal domain of the arrestin, making it possible for GPCRs that lack the C-terminal tail to couple Arr2 through their ICL3. Molecular dynamics simulation and crosslinking data further support the assembly of the Arr2-NTSR1 complex. Sequence analysis and homology modeling suggest that the Arr2-NTSR1 complex structure may provide an alternative template for modeling arrestin-GPCR interactions.

biophysics↗
bioRxiv2019

Robustness and lethality in multilayer biological molecular networks

Robustness is a prominent feature of most biological systems. In a cell, the structure of the interactions between genes, proteins, and metabolites has a crucial role in maintaining the cells functionality and viability in presence of external perturbations and noise. Despite advances in characterizing the robustness of biological systems, most of the current efforts have been focused on studying homogeneous molecular networks in isolation, such as protein-protein or gene regulatory networks, neglecting the interactions among different molecular substrates. Here we propose a comprehensive framework for understanding how the interactions between genes, proteins and metabolites contribute to the determinants of robustness in a heterogeneous biological network. We integrate heterogeneous sources of data to construct a multilayer interaction network composed of a gene regulatory layer, and protein-protein interaction layer and a metabolic layer. We design a simulated perturbation process to characterize the contribution of each gene to the overall systems robustness, defined as its influence over the global network. We find that highly influential genes are enriched in essential and cancer genes, confirming the central role of these genes in critical cellular processes. Further, we determine that the metabolic layer is more vulnerable to perturbations involving genes associated to metabolic diseases. By comparing the robustness of the network to multiple randomized network models, we find that the real network is comparably or more robust than expected in the random realizations. Finally, we analytically derive the expected robustness of multilayer biological networks starting from the degree distributions within or between layers. These results provide new insights into the non-trivial dynamics occurring in the cell after a genetic perturbation is applied, confirming the importance of including the coupling between different layers of interaction in models of complex biological systems.

systems biology↗
bioRxiv2019

Discovery of a celecoxib binding site on PTGES with a cleavable chelation-assisted biotin probe

The coxibs are a subset of non-steroidal anti-inflammatory drugs (NSAIDs) that primarily target cyclooxygenase-2 (COX-2) to inhibit prostaglandin signaling and reduce inflammation. However, mechanisms to inhibit other members of the prostaglandin signaling pathway may improve selectivity and reduce off-target toxicity. Here, we report a novel binding site for celecoxib on prostaglandin E synthase (PTGES), an enzyme downstream of COX-2 in the prostaglandin signaling pathway, using a cleavable chelation-assisted biotin probe 6. Evaluation of the multi-functional probe 6 revealed significantly improved tagging efficiencies attributable to the embedded picolyl functional group. Application of the probe 6 within the small molecule interactome mapping by photo-affinity labeling (SIM-PAL) platform using photo-celecoxib as a reporter for celecoxib identified PTGES and other membrane proteins in the top eight enriched proteins from A549 cells. Carbonic anhydrase 12, a known protein target of celecoxib, was also enriched. Four binding sites to photo-celecoxib were additionally mapped by the probe 6, including a binding site with PTGES. The binding interaction with PTGES was validated by competitive displacement with celecoxib and known PTGES inhibitor licofelone. The binding site of photo-celecoxib on PTGES enabled the development of a structural model of the interaction and will inform the design of new selective inhibitors of the prostaglandin signaling pathway.

pharmacology and toxicology↗
bioRxiv2019

Role of Chemokine and TNF signaling pathway in oral squamous cell carcinoma: A RNA deep sequencing analysis of oral buccal mucosa squamous carcinoma model of Chinese hamster

Oral cancer is one of the most common cancers in the world, meanwhile, differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas (OSCC). In this study we screened RNA transcripts from the oral buccal mucosa of healthy male Chinese hamster, divided into 3 groups: a control group with no disposal, a solvent control group coated with acetone solvent, and an experimental group coated with 0.5% DMBA acetone solution by high-throughput RNA sequencing. Tophat and Bowtie were used to align the high-quality reads into transcripts, DEseq was used to analysis the expression of differential gene. Then, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. The chemokine and TNF signaling pathway were differentially expression and the mRNA expression of CXCL1, CXCL2, CXCL3, CCL7, MMP9, monitored by qRT-PCR, increased remarkably in the cancer group and coincided with the result of RNA-Sequencing. Meanwhile, the CXCL1, CXCL2, CXCL3, and CCL7 are significantly enriched in the chemokine signaling pathway, and CXCL1, CXCL2, CXCL3, and MMP9 are significantly enriched in the tumor necrosis factor (TNF) signaling pathway. The differentially expression of the chemokine and TNF signaling pathway was a response to the invasion of the organism immune system due to oral buccal mucosa squamous carcinoma. All the findings provided novel insights for further molecular researches of oral cancer.

molecular biology↗