scholarly journals Interaction Between Functionally Activate Endometrial Microbiota and Host Gene Regulation in Endometrial Cancer

Author(s):  
Peigen Chen ◽  
Yingchun Guo ◽  
Lei Jia ◽  
Jing Wan ◽  
TianTian He ◽  
...  

Objective: In this study, we mainly explored two questions: Which microorganisms were functionally active in the endometrium of patients with endometrial cancer (EC)? What kind of response did the human host respond to functionally active microorganisms?Methods: Nine endometrial cancer patients and eight normal subjects were included in this study. HMP Unified Metabolic Analysis Network 3 (HUMAnN3) was used to obtain functional information of microorganisms. In addition, metaCyc-based GSEA functional enrichment analysis was used to obtain information on the metabolic pathways of the human host. At the same time, the O2PLS model and Spearman correlation analysis were used to analyze the microorganisms–host interaction.Results: With the novel metatranscriptome analysis pipeline, we described the composition of more than 5,000 functionally active microorganisms and analyzed the difference in microorganisms between the EC and the normal group. Our research found that these microorganisms were involved in part of the metabolic process of endometrial cancer, such as 6-sulfo-sialyl Lewis x epitope, N-acetyl-beta-glucosaminyl. In addition, the host–microbiota crosstalk of EC endometrium also included many biological processes, mainly functions related to tumor migration and the Apelin signaling pathway.Conclusion: The functionally active microorganisms in the EC endometrium played an essential role in the occurrence and migration of tumors. This meant that functionally active microorganisms could not be ignored in the treatment of endometrial cancer. This study helped to better understand the possible role of endometrial functional, active microorganisms in the occurrence and development of EC in patients with endometrial cancer and provided new information for new attempts to treat EC.

2021 ◽  
Vol 8 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Donghua Zou ◽  
Ling Huang ◽  
...  

Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes—s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjiao Cao ◽  
Wuyuan Gao ◽  
Panchan Zheng ◽  
Xiao Sun ◽  
Lihua Wang

Abstract Background Progestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB), further resulting in progestin resistance. Here, we performed microarray analysis on Ishikawa cells (PRB+) treated with medroxyprogesterone acetate (MPA) to explore the molecular mechanism underlying the inhibitory influence of MPA on PRB+ EC cells. Methods Microarray analysis was performed by using Ishikawa cells (PRB+) treated with MPA. Differentially expressed mRNA and long noncoding RNAs (lncRNAs) were identified. Furthermore, the functions of these mRNAs and lncRNAs were predicted by functional enrichment analysis. QRT-PCR was further performed to verify the microarray data. Results A total of 358 differentially expressed genes and 292 lncRNAs were identified in Ishikawa cells (PRB+) treated with MPA. QRT-PCR verified these data. Functional enrichment analysis identified endoplasmic reticulum (ER) stress as the key pathway involved in the inhibitory effect of MPA on EC cells. And the ER stress apoptotic molecule CHOP and ER stress related molecule HERPUD1 were both highly expressed in Ishikawa cells (PRB+) treated with MPA. Co-expression analysis showed lnc-CETP-3 was highly correlated with CHOP and HERPUD1, suggesting it might participate in ER stress pathway-related EC cell apoptosis caused by MPA. In addition, compared with untreated cells, lnc-CETP-3, CHOP and HERPUD1 were significantly up-regulated in Ishikawa cells (PRB+) treated with MPA, whereas they have no statistical significance in KLE cells (PRB-). Conclusions MPA may activate ER stress by progesterone-PRB pathway to up-regulate CHOP expression, which may be one of the molecular mechanisms underlying the inhibitory effect of MPA on EC cells with PRB+. Lnc-CETP-3 might be involved in this process. These findings may provide therapeutic targets for EC patients with PRB-, and resistance-related targets to increase the sensitivity of MPA on EC cells.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7882 ◽  
Author(s):  
Chao Wei ◽  
Jian-Jun Gao

Aim The study aims to identify differentially expressed microRNAs (DEMs) in gastric cancer (GC) and explore the expression, prognosis and downstream regulation role of miR-383-5p in GC. Methods The GC miRNA-Seq and clinical information were downloaded from Firebrowse which stores integrated data sourced from The Cancer Genome Atlas database. The DEMs were identified with limma package in R software at the cut-off criteria of P < 0.05 and |log2 fold change| > 1.0 (|log2FC| > 1.0). The expression of miR-383-5p in GC cell lines and 54 paired GC tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The overall survival curve of miR-383-5p and the association between its expression and clinicopathological features were explored. Wound healing and cell counting kit-8 assays were performed to investigate the capacity of miR-383-5p in cell proliferation and migration. The downstream target genes were predicted by bioinformatics tools (miRDB, TargetScan and starBase). The consensus target genes were selected for gene functional enrichment analysis by FunRich v3.0 software. The luciferase reporter assay was performed to verify the potential targeting sites of miR-383-5p on lactate dehydrogenase A (LDHA). Results A total of 21 down-regulated miRNAs (including miR-383-5p) and 202 up-regulated miRNAs were identified by analyzing GC miRNA-Seq data. Survival analysis found that patients with low miR-383-5p expression had a shorter survival time (median survival time 21.1 months) than those with high expression (46.9 months). The results of qRT-PCR indicated that miR-383-5p was downregulated in GC cell lines and tissues, which was consistent with miRNA-Seq data. The expression of miR-383-5p was significantly associated with tumor size and differentiation grade. Besides, overexpression of miR-383-5p suppressed GC cells proliferation and migration. A total of 49 common target genes of miR-383-5p were obtained by bioinformatics tools and gene functional enrichment analysis showed that these predicted genes participated in PI3K, mTOR, c-MYC, TGF-beta receptor, VEGF/VEGFR and E-cadherin signaling pathways. The data showed that expression of miR-383-5p was negatively correlated with target LDHA (r = −0.203). Luciferase reporter assay suggested that LDHA was a target of miR-383-5p. Conclusion The present study concluded that miR-383-5p was downregulated and may act as a tumor suppressor in GC. Furthermore, its target genes were involved in important signaling pathways. It could be a prognostic biomarker and play a vital role in exploring the molecular mechanism of GC.


2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  

Abstract Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects; (2) functional enrichment analysis and construction of differential methylation gene regulatory network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNA matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes-s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interested different expression positions (DMPS) and their corresponding gene expression, we found that the methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expression in obese subjects were validated in a separate microarray data set.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.


2021 ◽  
Author(s):  
Dou-Dou Ding ◽  
Quan Zhou ◽  
Ze He ◽  
Hong-Xia He ◽  
Man-Zhen Zuo

Abstract Introduction:Epidemiological studies have found that the occurrence of endometrial cancer(EC) is closely related to metabolic diseases, and insulin resistance (IR) plays an important role in the pathogenesis of endometrium, but the specific pathogenesis is still unclear. The purpose of this study is to reveal the relationship between insulin resistance and endothelial cells by gene screening technology. Material and methods:We analyzed one endometrial carcinoma database (GSE106191) and one insulin-resistant database (GSE63992), with Gene Expression Omnibus (GEO) database and Venny online analysis tool, then, we found an add-up to 148 different genes. Functional enrichment analysis of these genes using DAVID showed that they were participated in transcription factor activity,signaling pathways and response to factors, etc. Then used cytoHubba in Cytoscape,we got 25 hub genes.Results: The results showed that the survival time of OGT, IGSF3, TRO, NEURL2 and PIK3C2B was significantly and closely related to EC, and the percentage of gene changes of five central genes ranged from 3% to 10% of a single gene, was also related to the infiltration of seven kinds of immune cells in endometrial carcinoma.Conclusion:The five key genes (OGT,IGSF3, PIK3C2B,TRO and NEURL2) are involved in immune infiltration in the progression of endometrial carcinoma, and there is also a certain mutation probability in gene mutation. This may be the pathogenesis of insulin resistance and endometrial cancer.


2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  

Abstract Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects; (2) functional enrichment analysis and construction of differential methylation gene regulatory network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNA matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes-s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interested different expression positions (DMPS) and their corresponding gene expression, we found that the methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expression in obese subjects were validated in a separate microarray data set.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Li-yu Chen ◽  
Li-feng Zhang ◽  
Zhan-yuan Lu ◽  
Feng Xian ◽  
Jian-zhong Zhang ◽  
...  

Drought is a limiting factor for cotton productivity and quality. Irrigation could increase cotton yield. This study is aimed at formulating a proper irrigation depth for cotton at China’ Inner Mongolia and at investigating the molecular mechanism underlying the difference induced by irrigation. Transcriptomic analysis was carried out to reveal the global transcriptome profiles on the leaves of cotton seedlings (G. hirsutum L. cv. “Zhongmian 92”) with trace irrigation tapes at 30 cm (D30) and 50 cm (D50) underground. The differentially expressed genes (DEGs) were identified and clustered by functional enrichment analysis. The results showed that no significant differences were found in the lint percentage. The yields of unpinned and lint cotton were increased by the D30 regime but decreased by the D50 regime. Transcriptomic analysis showed that 4,549 nonoverlapped DEGs were identified by comparative analysis. Transcription factors, including bZIP, WARK, Myb, and NAC, were altered between D50 and D30. The D50 regime induced more DEGs compared with the D30 regime, which was associated with plant tolerance to abiotic stresses and drought. In conclusion, trace irrigation at 30 cm underground was suitable for cotton irrigation at China’s Inner Mongolia, while the D50 irrigation regime influenced the cotton yield via drought stress in cotton plants.


2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenyang Liao ◽  
Xunxiao Zhang ◽  
Shengcheng Zhang ◽  
Zhicong Lin ◽  
Xingtan Zhang ◽  
...  

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.


Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.


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