scholarly journals 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

2019 ◽  
Author(s):  
Guoqiang Xu ◽  
Jianing Wei ◽  
Bing Huangfu ◽  
Jiping Gao ◽  
Xiaotang Wang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Squamous Cell ◽  
Buccal Mucosa ◽  
Chinese Hamster ◽  
Squamous Carcinoma ◽  
Enrichment Analysis ◽  
Control Group ◽  
Sequencing Analysis

AbstractOral 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.

scholarly journals Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model

2020 ◽  
Vol 21 (21) ◽  
pp. 8171
Author(s):  
Ling-Yu Huang ◽  
Yi-Ping Hsieh ◽  
Yen-Yun Wang ◽  
Daw-Yang Hwang ◽  
Shih Sheng Jiang ◽  
...  
Keyword(s):  
Drinking Water ◽  
Oral Cancer ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Precancerous Lesions ◽  
Enrichment Analysis ◽  
Normal Mucosa ◽  
Gene Set Enrichment Analysis ◽  
Control Group ◽  
Sequencing Analysis

Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg/L) and arecoline (500 mg/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target.

scholarly journals Network Pharmacology and Experiment Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence

2021 ◽  
Author(s):  
Dianna Liu ◽  
Shicheng Lin ◽  
Yuan Li ◽  
Tian Zhou ◽  
Kaiwen Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Network Pharmacology ◽  
Phytochemical Analysis ◽  
Sequencing Analysis ◽  
Lewis Lung ◽  
Hub Genes

Abstract BackgroundLung adenocarcinoma (LUAD) is one of the most common malignancies with a rise in new cases worldwide each year. Recurrence significantly influences the survival in patients with LUAD. Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung cancer relapse by “nourishing yin and clearing heat”. MethodsIn this study, the mechanism of YHT in LUAD recurrence was investigated. Firstly, the bioactive compounds-targets network and the protein–protein interaction network were constructed, and functional annotation and pathway enrichment analyses were performed. Pivotal compounds and hub genes were selected from the networks. Subsequently, the effectiveness of YHT was confirmed in lewis lung carcinoma mice. RNA sequencing was used to explore the mRNA expression differences between tumor tissues in the model mouses and YHT-treated mouses. The pathways screened by network pharmacology and RNA sequencing analysis at the same time were considered the most important pathways. At last, qualitative phytochemical analysis, molecular docking technology, PCR and WB analysis were used to validate the pivotal active ingredients, hub genes and main pathways.ResultsThere were 128 active compounds, 419 targets interacting with LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Target genes mainly focused on inflammation, metabolism, immune responses and apoptosis. We confirmed that YHT could inhibit the recurrence of lung adenocarcinoma through animal experimental study. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub genes related with the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis of the water extract of YHT confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The results of molecular docking verified the pivotal compounds of YHT could good affinity with the S1PR5. The PCR and WB analysis verified YHT suppressed lewis lung cancer cells proliferation by inhibiting S1P/S1PR5/Gi/Ras/Raf/MEK/ERK pathway, and inhibited migration through S1P/S1PR5/Gi/PI3K/RAC pathway.ConclusionThe results confirmed the therapeutic effect of YHT on the recurrence of LUAD by multi-component-multi-target mode, the sphingolipid signaling pathway was one of the most relevant potential signaling pathways.

scholarly journals MicroRNA expression profiling involved in Borax-induced anti-tumor effect using gene-chip analysis

2020 ◽  
Author(s):  
Lun Wu ◽  
Ying Wei ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Li-Hua Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Enrichment Analysis ◽  
Gene Chip ◽  
Differentially Expressed ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Therapeutic Benefits ◽  
Differentially Expressed Mirnas

Abstract Background Borax, a boron compound, which is becoming widely recognized for its biological effects, including antioxidant activity, cytotoxicity, and potential therapeutic benefits. However, the specific molecular mechanisms underlying borax-induced anti-tumor effect still remain to be to further elucidated. MicroRNAs (miRNAs) may play key roles in cellular processes including tumor progression, cell apoptosis and cytotoxicity. Thus, this study aimed to investigate, whether miRNAs were involved in the borax-mediated anti-tumor effect using miRNA profiling of a human liver cancer cell line (HepG2) using gene-chip analysis.Methods Total RNA was extracted and purified from HepG2 cells that were treated with 4 mM borax for either 2 or 24 h. The samples underwent microarray analysis using an Agilent Human miRNA Array. Differentially expressed miRNAs were analysed by volcano plot and heatmap, and were validated using real-time fluorescent quantitative PCR (qPCR).ResultsAmong this, 2- or 24-h exposure to borax significantly altered the expression level of miRNAs in HepG2 cells, 4 or 14 were upregulated and 3 were downregulated compared with the control group, respectively (≥2-fold; P<0.05). GO enrichment analysis and KEGG pathway enrichment analysis revealed that target genes of differentially expressed miRNAs in HepG2 cells predominantly participated in MAPK signaling pathway, TGF-beta signaling pathway, NF-kappa B signaling pathway, etc; in 2-h borax treatment group, while Ras signaling pathway, FoxO signaling pathway, Cellular senescence, etc; involved in 24-h treatment group.Conclusions Result indicates that borax-induced anti-tumor effect may be associated with alterations in miRNAs.

scholarly journals Utilizing Network Pharmacology to Explore the Possible Mechanism of Coptidis Rhizoma in Kawasaki Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Xue Fan ◽  
Xin Guo ◽  
Ying Li ◽  
Mingguo Xu
Keyword(s):  
Kawasaki Disease ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Receptor Protein ◽  
Network Pharmacology ◽  
Control Group ◽  
Coptidis Rhizoma

Background: The purpose of the research is to identify the main active ingredients in Coptidis Rhizoma (CR) and explore the possible molecular mechanisms in the treatment of Kawasaki disease (KD).Materials and Methods: A total of 58 children with KD were randomly divided into a control group and a Berberine treatment group. The therapeutic indicators of the two groups before and after treatment were compared. Then, compounds and drug targets of CR from the TCMSP, SWISS, SEA, and the STITCH were collected, and targeted KD genes were retrieved from the DisGeNET, DrugBank, and GeneCards databases. The network pharmacology approach involved network construction, target prediction, and module analysis. GO and KEGG enrichment analysis were performed to investigate the possible pathways related to CR for KD treatments. Finally, protein expression was determined to verify the core targets using Western blotting in the cell experiment.Results: In total, nine compounds, 369 relative drug targets, and 624 KD target genes were collected in the above database. The network analysis revealed that 41 targets might be the therapeutic targets of CR on KD. GO and KEGG enrichment analysis revealed that the biological processes, namely, response to hormone, response to inorganic substance, and enzyme-linked receptor protein signaling pathway, and Pathways in cancer, Toll-like receptor signaling pathway, and Pancreatic cancer are the most significant. Protein expression of CASP3, PTGS2, and SRC was upregulated and AKT1 and ERK were downregulated.Conclusion: We provided useful resources to understand the molecular mechanism and the potential targets for novel therapy of KD.

scholarly journals Oral Cancer Senario in Multiple Centers of Dhaka, Bangladesh

2020 ◽  
Vol 5 (11) ◽  
pp. 572-575
Author(s):  
Dr. Rajesh Sah ◽  
Dr. Mahmuda Akhter
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Buccal Mucosa ◽  
Scientific Data ◽  
Treatment Modalities ◽  
Histopathological Diagnosis ◽  
Data Collection Sheet ◽  
The Common

Oral cancer is one of the common cancers worldwide and in Bangladesh around 7000 cases are diagnosed yearly. It has variable demographics and patient comes to hospital with different presentations. It is mandatory to know the characteristics of the disease so that better awareness and different treatment modalities can be planned. 162 patients with histopathological diagnosis of oral cancer was include in study by consecutive sampling and characteristics of disease was recorded in scientific data collection sheet which was later analyzed by SPSS and result was presented in table, graph and chart form. Incidence of oral cancer is 56.2% in female, in 59.9% cases buccal mucosa is involved in which 90.1% is squamous cell carcinoma. In Conclusion squamous cell carcinoma is most common oral cancer mainly occurs in buccal mucosa of female, in grade I and stage iii majority of patient present in tertiary centers of Dhaka.

scholarly journals Identification of lysine acetylome of oral squamous cell carcinoma by label-free quantitative proteomics

2021 ◽  
Author(s):  
Jingjing Dong ◽  
Jingquan He ◽  
Zeyu Zhang ◽  
Wei Zhang ◽  
Yixi Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cellular Response ◽  
Enrichment Analysis ◽  
Lysine Acetylation ◽  
Label Free ◽  
Normal Tissues

Abstract Background Lysine acetylation (Kac) favors gene transcription and activates various genes involved in the regulation of oncogenesis, whereas the acetylation profiling of oral squamous cell carcinoma (OSCC) is unknown. We performed lysine acetylation analyses to achieve a comprehensive profile and revealed the specific pathogenesis in patients with OSCC. Methods Liquid chromatography − tandem mass spectrometry (LC-MS/MS) was utilized to investigate lysine acetylation features of tumor tissues and adjacent normal tissues from 9 patients with OCSS. Results Among the upregulated different acetylation proteins (DAPs), the biological process of GO analysis was closely related to cellular response to regulation of apoptotic process, and regulation of programmed cell death. KEGG enrichment analysis was associated with HIF-1 signaling pathway, ferroptosis, and JAK-STAT signaling pathway. In PPI network, seven differently Kac proteins (SRSF1, HNPNPM, PRPF8, DHX9, DHX15, RBMX, SNRPG) in MCODE1 and the top 30 hub gene involved in mRNA splicing process and spliceosome pathway. Six differently Kac modified proteins of RPS15A, RPL11, RPS11, RPS3, RPL24, RPL19 in MCODE1 was enriched in ribosome pathway, particular lower expression of RPS3, RPL24 and RPL19 were related to the overall survival of OSCC. Conclusion This study contributes a foundation for understanding the functions of Kac modification in OSCC and investigates lysine acetylation on proteins involved in ribosome pathway, particularly the ones that acted as hub genes and related to the OSCC survival, which may be a potential therapeutic direction of OSCC in the future.

RhoC Mediates Invasion and Migration of CaSki Cells Through the Rho-Associated Serine-Threonine Protein Kinase 1 Signaling Pathway

2014 ◽  
Vol 24 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Rong Chen ◽  
Yuan Cheng ◽  
Youyi Zhang ◽  
Zijian Li ◽  
Li Geng
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Kinase ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Cervical Squamous Cell Carcinoma ◽  
Control Group ◽  
Invasion And Migration ◽  
And Migration

ObjectiveThe small GTPase RhoC in human cancers is up-regulated and correlated with tumor metastasis. However, the role of Rho/Rho-associated serine-threonine protein kinase 1 (ROCK1) signaling pathway in human cervical cancer is still unclear. In this study, we examine the effects of RhoC and its major downstream target, ROCK1, on the invasion and migration of CaSki cells to investigate the role of RhoC/ROCK1 signaling pathway in the progression of cervical squamous cell carcinoma.MethodsRhoC and ROCK1 protein expression in CaSki cells was detected by Western blotting. Scratch and transwell assays were carried out to assess the effects of RhoC on invasion and migration of CaSki cells. Cell viability was assayed by MTT test after adding the ROCK1 inhibitor Y-27632 to CaSki cells.ResultsOverexpression of RhoC protein in CaSki cells significantly increases ROCK1 expression and promotes cell invasion and migration compared with the control group (P< 0.05). However, in the inhibition of ROCK1 with Y-27632 in CaSki cells when RhoC was overexpressed, the rate of invasiveness and migration was reduced remarkably (P< 0.05), dropping to comparable levels as the control.ConclusionsThis study suggested that the activation of RhoC/ROCK1 signaling pathways is likely involved in the progression of cervical squamous cell carcinoma.

scholarly journals Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245749
Author(s):  
Zhuang Hao ◽  
Zhen Li ◽  
Jinjin Huo ◽  
Jiandong Li ◽  
Fenghua Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Enrichment Analysis ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Sequencing Analysis ◽  
Lycium Barbarum ◽  
Pig Liver ◽  
Antioxidant Genes ◽  
Tibetan Pig

The objective of this study is to determine the effect of Chinese wolfberry (Lycium barbarum) and Astragalus (Astragalus membranaceus) extract (WAE) on the antioxidant capacity of Tibetan pig liver, and discussed the regulatory effect of WAE on the liver antioxidant mechanism. Twelve healthy 120-day-old Tibetan black pigs (35±2 kg) were divided randomly into two groups. The WAE group was fed a basal diet supplemented with 1% WAE for 90 days. The control group was fed the same diet, but without the WAE. We found that liver superoxide dismutase 1 (SOD1) activity (P<0.05), total antioxidative capacity (T-AOC) (P<0.05), and catalase (CAT) activity (P<0.01) significantly increased in the WAE group compared with the control group; malondialdehyde (MDA) content decreased, but this was not significant (P >0.05). Transcriptome sequencing analysis detected 106 differentially expressed genes (DEGs) related to oxidative stress. GO enrichment analysis showed these DEGs were involved in the positive regulation of reactive oxygen metabolism and biosynthesis, process regulation, and regulation of the oxidative stress response. KEGG Pathway enrichment analysis showed they were enriched in the PI3K-Akt, AMPK, Rap1, and peroxisome signaling pathways. The expression levels of key peroxisome biosynthesis genes (e.g., PEX3 and PEX11B) and key antioxidant genes (e.g., CAT and SOD1) were significantly higher in the WAE group than in the control group. The PRDX1 and PRDX5 content also was significantly higher in the WAE group. This study showed that the WAE regulated the antioxidant and anti-stress ability of Tibetan pig liver through a “peroxisome antioxidant-oxidant stress” signaling pathway.

scholarly journals A Network Pharmacology-Based Approach to Investigating the Mechanisms of Fushen Granule Effects on Intestinal Barrier Injury in Chronic Renal Failure

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Miaoru Han ◽  
Hangxing Yu ◽  
Kang Yang ◽  
Panying Liu ◽  
Haifeng Yan ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Signaling Pathway ◽  
Intestinal Barrier ◽  
Enrichment Analysis ◽  
Control Group ◽  
T84 Cells ◽  
Protein Expressions ◽  
Group Protein ◽  
Cox 2

Purpose. Fushen Granule (FSG) is a Chinese medicine prepared by doctors for treating patients with chronic renal failure, which is usually accompanied by gastrointestinal dysfunction. Here, we explore the protective effect of FSG on intestinal barrier injury in chronic renal failure through bioinformatic analysis and experimental verification. Methods. In this study, information on the components and targets of FSG related to CRF is collected to construct and visualize protein-protein interaction networks and drug-compound-target networks using network pharmacological methods. DAVID is used to conduct gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, it is validated by in vitro experiments. In this study, the human intestinal epithelial (T84) cells are used and divided into four groups: control group, model group, FSG low-dose group, and FSG high-dose group. After the experiment, the activity of T84 cells is detected by a MTT assay, and the expressions of tight junction protein ZO-1, claudin-1, nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) are examined by immunofluorescence and/or western blotting. Results. Eighty-six potential chronic renal failure-related targets are identified by FSG; among them, nine core genes are screened. Furthermore, GO enrichment analysis shows that the cancer-related signaling pathway, the PI3K-Akt signaling pathway, the HIF1 signaling pathway, and the TNF signaling pathway may play key roles in the treatment of CRF by FSG. The MTT method showed that FSG is not cytotoxic to uremic toxin-induced injured T84 cells. The results of immunofluorescence and WB indicate that compared with the control group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is decreased and protein expressions level of HO-1, MDA, and COX-2 is increased after urinary toxin treatment. Instead, compared with the model group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is increased and protein expressions level of HO-1, MDA, and COX-2 is decreased after FSG treatment. Conclusion. FSG had a protective effect on urinary toxin-induced intestinal epithelial barrier injury in chronic renal failure, and its mechanism may be related to the upregulation of Nrf2/HO-1 signal transduction and the inhibition of tissue oxidative stress and inflammatory responses. Screening CRF targets and identifying the corresponding FSG components by network pharmacological methods is a practical strategy to explain the mechanism of FSG in improving gastrointestinal dysfunction in CRF.

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