scholarly journals Screening and Functional Analysis of Hub MicroRNAs Related to Tumor Development in Colon Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Dong-Hu Yu ◽  
Wei Li ◽  
Jing-Yu Huang ◽  
Xiao-Ping Liu ◽  
Chi Zhang ◽  
...  

Various microRNAs (miRNAs) are of importance in the development of colon cancer, but most of the mechanisms of the miRNAs are still unclear. In order to clarify the hub miRNAs and their roles in colon cancer development, GSE98406 was used to screen hub miRNAs by bioinformatics analysis. 46 DE-miRNAs (14 were upregulated and 32 were downregulated) and 1738 target genes of DE-miRNAs were ascertained. miRNAs-gene-networks and miRNAs-GO-networks were built to get more knowledge about the function of candidate miRNAs. After validation, three miRNAs (miR-17-5p, miR-182-5p and miR-200a-3p) were recognized to be hub miRNAs associated with the progression of colon cancer. More importantly, the hub miRNAs and the putative targets genes might be new diagnostic and therapeutic targets for colon cancer in the future.

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Shengtao Lin ◽  
Tao Jiang ◽  
Yang Yu ◽  
Huamei Tang ◽  
Su Lu ◽  
...  

Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experimentsin vitrovalidated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Harish Joshi ◽  
Basavaraj Vastrad ◽  
Nidhi Joshi ◽  
Chanabasayya Vastrad ◽  
Anandkumar Tengli ◽  
...  

Obesity is an excess accumulation of body fat. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Functional enrichment analysis was performed. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then protein–protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. The module analysis was performed based on the whole PPI network. We finally filtered out STAT3, CORO1C, SERPINH1, MVP, ITGB5, PCM1, SIRT1, EEF1G, PTEN and RPS2 hub genes. Hub genes were validated by ICH analysis, receiver operating curve (ROC) analysis and RT-PCR. Finally a molecular docking study was performed to find small drug molecules. The robust DEGs linked with the development of obesity were screened through the expression profile, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.


2020 ◽  
Author(s):  
Harish Joshi ◽  
Basavaraj Mallikarjunayya Vastrad ◽  
Nidhi Joshi ◽  
Anandkumar Tengli ◽  
Chanabasayya Mallikarjunayya Vastrad ◽  
...  

Abstract Obesity is the most common metabolic disorder worldwide. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Pathway enrichment analyses and Gene Ontology (GO) were performed by online tool ToppCluster. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then, the mentha, miRNet and NetworkAnalyst databases were used to construct the protein–protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network. The module analysis was performed by the PEWCC1 plug‐in of Cytoscape based on the whole PPI network. We finally filtered out HSPA8, ESR1, YWHAH, RPL14, SOD2, BTG2, LYZ and EFNA1 hub genes. Hub genes were validated by ICH analysis, Receiver operating curve (ROC) analysis and RT-PCR. Finally molecular docking study was performed. The robust DEGs linked with the development of obesity was screened through the ArrayExpress database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.


2021 ◽  
Author(s):  
Jin Wang ◽  
Lei Zhou ◽  
Bingxin Chen ◽  
Zhuwen Yu ◽  
Jianglei Zhang ◽  
...  

Abstract Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study investigated the role of a novel circular RNA (circCSPP1) in colon cancer and explored the possible underlying molecular mechanisms. Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer specimens and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, Transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1). It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. The overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas the silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression levels of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level. Notably, circCSPP1 from SW620 cells was transferred to macrophages via exosomes and enhanced the colon cancer microenvironment. Taken together, the findings of the present study indicated that circCSPP1 may functions as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.


2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Ruixue Chen ◽  
Minghao Chen ◽  
Ya Xiao ◽  
Qiuer Liang ◽  
Yunfei Cai ◽  
...  

In traditional Chinese medicine (TCM), blood stasis syndrome (BSS) is mainly manifested by the increase of blood viscosity, platelet adhesion rate and aggregation, and the change of microcirculation, resulting in vascular endothelial injury. It is an important factor in the development of diabetes mellitus (DM). The aim of the present study was to screen out the potential candidate microRNAs (miRNAs) in DM patients with BSS by high-throughput sequencing (HTS) and bioinformatics analysis. Human umbilical vein endothelial cells (HUVECs) were incubated with 10% human serum to establish models of DM with BSS, DM without BSS (NBS), and normal control (NC). Total RNA of each sample was extracted and sequenced by the Hiseq2000 platform. Differentially expressed miRNAs (DE-miRNAs) were screened between samples and compared with known changes in mRNA abundance. Target genes of miRNAs were predicted by softwares. Gene Ontology (GO) and pathway enrichment analysis of the target genes were conducted. According to the significantly enriched GO annotations and pathways (P-value ≤ 0.001), we selected the key miRNAs of DM with BSS. It showed that the number of DE-miRNAs in BSS was 32 compared with non-blood stasis syndrome (NBS) and NC. The potential candidate miRNAs were chosen from GO annotations in which target genes were significantly enriched (−log10 (P-value) > 5), which included miR-140-5p, miR-210, miR-362-5p, miR-590-3p, and miR-671-3p. The present study screened out the potential candidate miRNAs in DM patients with BSS by HTS and bioinformatics analysis. The miRNAs will be helpful to provide valuable suggestions on clinical studies of DM with BSS at the gene level.


2020 ◽  
Author(s):  
Qiang Ma

Abstract Background: Primary central nervous system lymphoma (PCNSL), a rare form of the non-Hodgkin's lymphoma (NHL), usually has a poor prognosis, and molecular pathogenesis of PCNSL has not been fully elucidated. Here, potential miRNA biomarkers were investigated in patients with PCNSL using an integrated bioinformatics analysis. Methods: Expression profile arrays (GSE122011, GSE139031, and GSE25297) were obtained from the Gene Expression Omnibus (GEO). Free-scale miRNA co-expression networks were constructed with 27 PCNSL patients from GSE122011 by the weighted gene co-expression network analysis (WGCNA) in order to identify candidate biomarkers. Subsequently, miRNA-miRNA networks were visualized with the Cytoscape. Expression of candidate miRNAs was assessed in serum samples from GSE139031, including 42 PCNSL patients and 77 non-cancer individuals, and the sensitivity and the specificity were assessed by the receiver operating characteristic (ROC) curve. From GSE25297, differentially expressed genes (DEGs) from the PCNSL tissues (n = 7) and the normal lymph nodes (n = 7) were compared, target genes of candidate miRNAs were downloaded from TargetScan database, and target genes that were also down-regulated in GSE25297 were used to construct the protein-protein interaction (PPI) networks and for the gene ontology (GO) analysis. Results: miRNAs were clustered into two groups with 8 modules in 27 patients with PCNSL. One group consisted of the yellow and the turquoise modules, and the second group consisted of the other six modules. In the miRNA-miRNA network, the highest nodes were observed between miR-432 and miR-330-3p, which were from the yellow and the turquoise modules, and only miR-432 was closely associated with both the yellow (0.977, P = 2.88E -18 ) and the turquoise modules (0.525, P = 0.005). Additionally, patients with PCNSL had higher serum miR-432 expression compared with that in the non-cancer controls in GSE139031, and miR-432 has a higher accuracy for discriminating between PCNSL and non-cancer samples (AUC: 0.77; 95% CI: 0.6923 to 0.8550). For target genes of miR-432, RASGRF , DGKG , SMIM22 , SPOCD1 , NRCAM , CNTN2 , PTPRD , POTED , IGSF3 , SLC24A2 , CTNND2 , AIF1L , TMEM229A , GLDN , and MOBP were down-regulated in the PCNSL tissues. Among them, CTNND2 , GLDN , NRCAM , and PTPRD were associated with cell adhesion. Conclusion: Up-regulated miR-432 expression is a novel biomarker for patients with PCNSL and may be associated with cell adhesion.


Author(s):  
Ryou-u Takahashi ◽  
Marta Prieto-Vila ◽  
Ai Hironaka ◽  
Takahiro Ochiya

AbstractmicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. miRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells. In addition to cellular miRNAs (ce-miRNAs), secreted miRNAs (se-miRNAs) play important roles in cancer development and metastasis. Therefore, se-miRNAs in body fluids have been investigated as a promising biomarkers and therapeutic targets for cancer treatment. In this review, we summarize the current knowledge of miRNA functions in cancer development and discuss the potential clinical applications of se-miRNAs, e.g. as diagnostic markers and therapeutic targets.


Author(s):  
Dr. Joanne R. Lupton ◽  
Dr. Nancy D. Turner ◽  
Dr. Leslie Braby ◽  
Dr. John Ford ◽  
Dr. Raymond J. Carroll ◽  
...  

2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.


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