scholarly journals Effects of Different Molecular Weight Polysaccharides From Dendrobium officinale Kimura & Migo on Human Colorectal Cancer and Transcriptome Analysis of Differentially Expressed Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Shengchang Tao ◽  
Zhiyao Ren ◽  
Zerui Yang ◽  
Shuna Duan ◽  
Zhongxian Wan ◽  
...  

We investigated the antitumor effects of four fractions of Dendrobium officinale Kimura & Migo (D. officinale) polysaccharides with different molecular weights (Mw), Astragalus membranaceus polysaccharides (APS) and Lentinus edodes polysaccharides (LNT) on colorectal cancer (CRC) using a zebrafish xenograft model. Transcriptome sequencing was performed to further explore the possible antitumor mechanisms of D. officinale polysaccharides. Fractions of D. officinale polysaccharides, LNT, and APS could significantly inhibit the growth of HT-29 cells in a zebrafish xenograft model. One fraction of D. officinale polysaccharides called DOPW-1 (Mw of 389.98 kDa) exhibited the strongest tumor inhibition. Compared with the control group, RNA-seq revealed that the DOPW-1–treated experimental group had 119 differentially expressed genes (DEGs), of which 45 had upregulated expression and 74 had downregulated expression. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes suggested that the pathway “apoptosis-multiple species” was the most significantly enriched. Our data indicated that 1) fractions of D. officinale polysaccharides of Mw 389.98 kDa were most suitable against CRC; 2) DOPW-1 could be developed into a clinical agent against CRC; and 3) an apoptosis pathway is important for DOPW-1 to inhibit the proliferation of HT-29 cells.

2021 ◽  
pp. 100995
Author(s):  
Shengchang Tao ◽  
Chunlei Huang ◽  
Zhihong Tan ◽  
Shuna Duan ◽  
Xiaofeng Zhang ◽  
...  

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 165-166
Author(s):  
Elisa B Carvalho ◽  
Letícia P Sanglard ◽  
Karolina B Nascimento ◽  
Javier M Meneses ◽  
Daniel R Casagrande ◽  
...  

Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Chaoqun Xing ◽  
Zhi Huang ◽  
Jing Peng ◽  
...  

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.


2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Su ◽  
Yu-qiao Gao ◽  
Wei-bo Dai ◽  
Ying Hu ◽  
Yan-fen Wu ◽  
...  

Colorectal cancer (CRC) is one of the most common malignancies and most frequent cause of cancer death worldwide. The activation of both NF-κB and STAT3 signaling and the crosstalk between them play an important role in colorectal tumor.Helicteres angustifoliaL. is a type of commonly used Chinese medicinal herb and possesses a wide variety of biological activities. In the present study, we investigate the effects of three triterpenes fromH. angustifolia(HT) such as helicteric acid (HA), oleanic acid (OA), and betulinic acid (BA), on inhibiting CRC progression. Our results showed that HT extracts could decrease proliferation and induce apoptosis in HT-29 colorectal cancer cells. Moreover, HT extracts could suppress LPS-triggered phosphorylation of IKK, IκB, and NF-κB, attenuate IL-6-induced phosphorylation of JAK2 and STAT3, and suppress the expression of c-Myc, cyclin-D1, and BCL-xL, the downstream gene targets of NF-κB and STAT3. Therefore, HT extracts showed potent therapeutic and antitumor effects on CRC via inhibiting NF-κB and STAT3 signaling.


2009 ◽  
Vol 4 ◽  
pp. BMI.S2530 ◽  
Author(s):  
Salah A. Mohamed ◽  
Hans H. Sievers ◽  
Thorsten Hanke ◽  
Doreen Richardt ◽  
Claudia Schmidtke ◽  
...  

Background Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk. Materials and Methods Aortic tissue was collected from 19 patients with AAD (mean age 61.7 ± 13.1 years), and from eight other patients (mean age 32.9 ± 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 ± 12.3 years) served as the control group. The PIQOR™ Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using PathwayAssist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed. Results Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 ± 0.4 vs. 6.1 ± 2.3 fold, p = 0.003) and of DCN (2.5 ± 1.0 vs. 8.5 ± 4.7 fold, p = 0.04) in AAD compared to MS and control samples. Conclusions Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.


2015 ◽  
Vol 112 (25) ◽  
pp. 7743-7748 ◽  
Author(s):  
Muhammad Akhtar Ali ◽  
Shady Younis ◽  
Ola Wallerman ◽  
Rajesh Gupta ◽  
Leif Andersson ◽  
...  

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle–related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.


2019 ◽  
Author(s):  
De Peng Yuan ◽  
Chong Zhang ◽  
Si Ting Wang ◽  
Yang Liu ◽  
Shuang Li ◽  
...  

Abstract Background: Sheath blight disease (ShB) is one of the important diseases that severely affects rice production. However, the mechanism of defense against ShB remains unclear. To understand the molecular mechanism of rice defense to ShB, an RNA-sequencing analysis was performed using Rhizoctonia solani AG1-IA-inoculated rice leaves. Results: After 48 hours of inoculation, 6,838 genes were differentially expressed in rice leaves (>2 fold, P<0.05). Among them, 3,802 genes were upregulated, while 3,036 were downregulated compared to the control group. In addition, the differentially expressed genes were classified via GO, KEGG, and Mapman analyses. Thirty GO terms, including biological process, molecular function, and cellular component, were significantly enriched, and 30 KEGG pathways included ribosome, carbon metabolism, and biosynthesis of amino acids. A Mapman analysis demonstrated that the phytohormone and metabolic pathways were significantly altered. Interestingly, the expression levels of 359 transcription factors, including WRKY, MYB, and NAC family members, as well as 239 transporter genes, including ABC, MFS, and SWEET, were significantly changed upon R. solani AG1-IA inoculation. An additional genetic study showed that OsWRKY53 negatively and OsAKT1 positively regulate rice defense to R. solani, respectively. In addition, interestingly, many differentially expressed genes contain R. solani-responsive cis-elements in their promoter region. Conclusions: Taken together, our analyses provide valuable information for the additional study of rice defense mechanisms to ShB, and the genes identified could be useful in the future to breed resistant rice.


2020 ◽  
Author(s):  
Yuqing Yang ◽  
Ting Sun ◽  
Chuchen Qiu ◽  
Dongjing Chen ◽  
You Wu

ABSTRACTBackgroundGlioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.MethodsThe gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.ResultsOur investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.ConclusionFPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.


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