Analysis of Overexpressed miRNA in Circulation and Cancer Tissue to Develop a Potential microRNA Panel for the Diagnosis of Colorectal Cancer

MicroRNA ◽  
2021 ◽  
Vol 11 ◽  
Author(s):  
Babita Pruseth ◽  
Amit Ghosh ◽  
Dibyabhaba Pradhan ◽  
Suvendu Purkait ◽  
Praveen Kumar Guttula
Keyword(s):  
Colorectal Cancer ◽  
Metal Ion ◽  
Target Genes ◽  
Target Identification ◽  
Gene Expression Omnibus ◽  
Vital Role ◽  
Cancer Tissue ◽  
Success Rates ◽  
Metal Ion Binding ◽  
Serum Samples

Background: Colorectal cancer (CRC) represents the world’s fourth deadly cancer, but its early diagnosis can be curative with considerable success rates. This study was aimed to identify CRC specific microRNAs (miRNAs) in tissue and serum samples to develop a miRNA-based diagnostics panel for the minimal invasive detection of CRC in early condition. Methods: By integrating four microarrays in tissue and serum samples of CRC from Gene Expression Omnibus (GEO) database, we screened out the highly expressed miRNAs in each dataset by using limma R package. Two important upregulated miRNAs namely hsa-miR-1246 and hsa-miR-1825 were overlapped in both tissue and serum samples of CRC, and were investigated to target identification, followed by functional annotation and protein- protein interaction (PPI) study for the target genes through DAVID and STRING respectively. Finally, hub target genes were retrieved by Cytoscape analysis. Results: It was shown that target genes of hsa-miR-1246 and hsa-miR-1825 were involved with core KEGG pathways (such as cAMP, PI3K-Akt and calcium signaling pathway). In addition, biological processes (such as cell adhesion and cell proliferation), cellular components (such as plasma membrane and cytosol), molecular functions (such as protein binding and metal ion binding), were mostly associated with the target genes. Their top 5 target genes were retrieved and their biological function towards tumor progression was shown using Cancer Hallmarks Analytics Tool. Conclusion: This study suggested that hsa-miR-1246 and hsa-miR-1825, as overlapped upregulated tissue and circulating miRNAs might have a vital role in the development of CRC and their five hub target genes were identified.

GLOBAL METAL-ION BINDING PROTEIN FINGERPRINT: A METHOD TO IDENTIFY MOTIF-LESS METAL-ION BINDING PROTEINS

2010 ◽  
Vol 08 (04) ◽  
pp. 717-726 ◽  
Author(s):  
ABHILASH MOHAN ◽  
SHARMILA ANISHETTY ◽  
PENNATHUR GAUTAM
Keyword(s):  
Metal Ion ◽  
Binding Proteins ◽  
Binding Protein ◽  
Vital Role ◽  
Ion Binding ◽  
Binding Motif ◽  
Specific Class ◽  
Metal Ion Binding ◽  
Knowledge Based ◽  
Supervised Classifiers

Metal-ion binding proteins play a vital role in biological processes. Identifying putative metal-ion binding proteins is through knowledge-based methods. These involve the identification of specific motifs that characterize a specific class of metal-ion binding protein. Metal-ion binding motifs have been identified for the common metal ions. A robust global fingerprint that is useful in identifying a metal-ion binding protein from a non-metal-ion binding protein has not been devised. Such a method will help in identifying novel metal-ion binding proteins and proteins that do not possess a canonical metal-ion binding motif. We have used a set of physico-chemical parameters of metal-ion binding proteins encoded by the genes CzcA, CzcB and CzcD as a training set to supervised classifiers and have been able to identify several other metal ion binding proteins leading us to believe that metal-ion binding proteins have a global fingerprint, which cannot be pinned down to a single feature of the protein sequence.

scholarly journals Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Qiaowei Fan ◽  
Lin Guo ◽  
Jingming Guan ◽  
Jing Chen ◽  
Yujing Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
R Package ◽  
Gastrointestinal Diseases ◽  
Gene Expression Omnibus ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ppi Network

Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. Conclusion. The study elucidated the “multiingredient, multitarget, and multipathway” mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.

scholarly journals miRNA Clusters with Up-Regulated Expression in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2979
Author(s):  
Paulína Pidíková ◽  
Iveta Herichová
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Expression Patterns ◽  
Clinicopathological Characteristics ◽  
Cancer Tissue ◽  
Poor Patient ◽  
Regulated Expression ◽  
Mirna Clusters ◽  
Non Coding Rnas ◽  
Poor Patient Survival

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.

scholarly journals MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Xueyang Cui ◽  
Zhi Lv ◽  
Hanxi Ding ◽  
Chengzhong Xing ◽  
Yuan Yuan
Keyword(s):  
Colorectal Cancer ◽  
Bioinformatics Analysis ◽  
Diagnostic Value ◽  
Cancer Tissue ◽  
Serum Samples ◽  
Ki 67 ◽  
Diagnostic Efficacy ◽  
Expression Levels ◽  
Potential Biomarker ◽  
Endothelial Growth Factor

PurposeWe investigated microRNA (miR) 1539 as a potential biomarker for predicting the risk and pathobiological behavior of colorectal cancer (CRC).MethodsOur strategy consisted of analyzing 100 serum samples from 51 CRC patients, 49 healthy controls (HCs), and another 56 CRC tissue and matched normal adjacent to tumor (NAT) samples. The relative expression levels of miR-1539 in exosomes, serum and tissues were detected and compared in the different groups, using reverse transcription-polymerase chain reaction (RT-qPCR). The diagnostic value and potential function of miR-1539 were investigated using clinicopathological data combined with bioinformatics analysis.ResultsMiR-1539 expression was significantly up-regulated in exosomes (p = 0.003) and cancer tissue (p < 0.001) from CRC patients. MiR-1539 expression levels in serum varied according to different tumor sites (right-sided vs. left-sided, p = 0.047; left-side CRC vs. HCs, p = 0.031). In terms of diagnostic efficacy, miR-1539 expression in exosomes may help distinguish CRC cases from HCs with a sensitivity of 92.2%, and miR-1539 expression in serum may improve the specificity to 96.6% for left-sided CRC diagnosis. When combined with clinicopathological data, serum miR-1539 levels were positively associated with vascular endothelial growth factor (VEGF) expression (p = 0.028), whilst levels in CRC tissue were positively associated with increased Ki-67 levels (p = 0.035). Poorer pathologic differentiation was potentially related to an increased tendency of miR-1539 expression in CRC tissue (p = 0.071). Based on our bioinformatics analysis, miR-1539 may have a significant mechanistic influence on CRC genesis and progression.ConclusionsCirculating or tissue based miR-1539 may be used as a novel potential biomarker for CRC screening, and a predictor of poor clinicopathological behavior in tumors.

scholarly journals Comparative Transcriptomics Analysis of Testicular miRNA from Cryptorchid and Normal Horses

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 338
Author(s):  
Haoyuan Han ◽  
Qiuming Chen ◽  
Yuan Gao ◽  
Jun Li ◽  
Wantao Li ◽  
...  
Keyword(s):  
Metal Ion ◽  
Target Genes ◽  
Expression Patterns ◽  
Osteoclast Differentiation ◽  
Zinc Ion ◽  
Differentially Expressed ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Expression Levels ◽  
Differentially Expressed Mirnas

In the biological process of testicular spermatogenesis, the expression and interaction of many genes are regulated by microRNAs (miRNAs). However, comparisons of miRNA expression between descended testes (DTs) and undescended testes (UDTs) are rarely done in horses. In this study, we selected two UDTs (CKY2b and GU4b) from Chakouyi (CKY) and Guanzhong (GU) horses and eight DTs (GU1–3, CKY1, CKY3, CKY2a, GU4a, and GU5). Three groups were compared to evaluate expression patterns of testicular miRNA in stallion testes. Group 1 compared normal CKY horses and GU horses (CKY1 and CKY3 vs. GU1–3). Group 2 (CKY2a and GU4a (DTs) vs. CKY2b and GU4b (UDTs)) and group 3 (GU1–3, CKY1, CKY3 (DTs) vs. CKY2b and GU4b (UDTs)) compared the expression levels in unilateral retained testes to normal testes. The results show that 42 miRNAs (7 upregulated and 35 downregulated) had significantly different expression levels in both comparisons. The expression levels of eca-miR-545, eca-miR-9084, eca-miR-449a, eca-miR-9024, eca-miR-9121, eca-miR-8908e, eca-miR-136, eca-miR-329b, eca-miR-370, and eca-miR-181b were further confirmed by quantitative real-time PCR assay. The target genes of differentially expressed miRNAs in three comparisons were predicted, and the functions were annotated. The putative target genes of the 42 co-differentially expressed miRNAs were annotated to 15 functional terms, including metal ion binding, GTPase activator activity, zinc ion binding, intracellular, cytoplasm, and cancer pathways, and osteoclast differentiation. Our data indicate that the differentially expressed miRNAs in undescended testis suggests a potential role in male fertility and a relationship with cryptorchidism in horses. The discovery of miRNAs in stallion testes might contribute to a new direction in the search for biomarkers of stallion fertility.

A Review on Theragnostic Applications of Micrornas and Long Non- Coding RNAs in Colorectal Cancer

2019 ◽  
Vol 18 (30) ◽  
pp. 2614-2629 ◽  
Author(s):  
Ganesan Jothimani ◽  
Sushmitha Sriramulu ◽  
Yashna Chabria ◽  
Xiao-Feng Sun ◽  
Antara Banerjee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Fate ◽  
Target Identification ◽  
Vital Role ◽  
Novel Approach ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Median Survival Rate

Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.

miR-432 is a novel biomarker for PCNSL and is associated with cell adhesion: An integrated bioinformatics analysis

2020 ◽  
Author(s):  
Qiang Ma
Keyword(s):  
Cell Adhesion ◽  
Operating Characteristic ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Central Nervous System Lymphoma ◽  
Gene Expression Omnibus ◽  
Serum Samples ◽  
Protein Protein Interaction ◽  
Candidate Mirnas ◽  
Ppi Networks

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.

scholarly journals MicroRNA Omics Analysis of Camellia sinesis Pollen Tubes in Response to Low-Temperature and Nitric Oxide

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 930
Author(s):  
Xiaohan Xu ◽  
Weidong Wang ◽  
Yi Sun ◽  
Anqi Xing ◽  
Zichen Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Wall ◽  
Low Temperature ◽  
Metal Ion ◽  
Target Genes ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Omics Analysis ◽  
Cell Wall Organization ◽  
Signal Network

Nitric oxide (NO) as a momentous signal molecule participates in plant reproductive development and responds to various abiotic stresses. Here, the inhibitory effects of the NO-dominated signal network on the pollen tube growth of Camellia sinensis under low temperature (LT) were studied by microRNA (miRNA) omics analysis. The results showed that 77 and 71 differentially expressed miRNAs (DEMs) were induced by LT and NO treatment, respectively. Gene ontology (GO) analysis showed that DEM target genes related to microtubules and actin were enriched uniquely under LT treatment, while DEM target genes related to redox process were enriched uniquely under NO treatment. In addition, the target genes of miRNA co-regulated by LT and NO are only located on the cell membrane and cell wall, and most of them are enriched in metal ion binding and/or transport and cell wall organization. Furthermore, DEM and its target genes related to metal ion binding/transport, redox process, actin, cell wall organization and carbohydrate metabolism were identified and quantified by functional analysis and qRT-PCR. In conclusion, miRNA omics analysis provides a complex signal network regulated by NO-mediated miRNA, which changes cell structure and component distribution by adjusting Ca2+ gradient, thus affecting the polar growth of the C. sinensis pollen tube tip under LT.

MicroRNAs and their role in hematological malignant diseases

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Cancer Tissue ◽  
Altered Expression ◽  
Diagnosis And Prognosis ◽  
Oncologic Patients ◽  
Different Types ◽  
Non Coding Rnas ◽  
Success Of Treatment ◽  
Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

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