Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K–Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein–protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K–Akt–mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

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STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway

Neoplasia ◽

10.1016/j.neo.2021.05.011 ◽

2021 ◽

Vol 23 (6) ◽

pp. 607-623

Author(s):

Hui Xu ◽

Xiaomei Yang ◽

Xiaofeng Xuan ◽

Di Wu ◽

Jieru Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway

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Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.10470 ◽

2021 ◽

Vol 9 ◽

pp. e10470

Author(s):

Wanzhen Li ◽

Shiqing Liu ◽

Shihong Su ◽

Yang Chen ◽

Gengyun Sun

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Target Genes ◽

Predictive Accuracy ◽

Differentially Expressed ◽

Prognostic Signature ◽

Tissue Samples ◽

Gene Set ◽

Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

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Integration of a Systems Biological Network Analysis and QTL Results for Biomass Heterosis in Arabidopsis thaliana

PLoS ONE ◽

10.1371/journal.pone.0049951 ◽

2012 ◽

Vol 7 (11) ◽

pp. e49951 ◽

Cited By ~ 3

Author(s):

Sandra Andorf ◽

Rhonda C. Meyer ◽

Joachim Selbig ◽

Thomas Altmann ◽

Dirk Repsilber

Keyword(s):

Arabidopsis Thaliana ◽

Network Analysis ◽

Biological Network ◽

Biological Network Analysis

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Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis

Lupus ◽

10.1177/09612033211061482 ◽

2021 ◽

pp. 096120332110614

Author(s):

Yan Liang ◽

Ji Zhang ◽

Wenxian Qiu ◽

Bo Chen ◽

Ying Zhou ◽

...

Keyword(s):

Lupus Nephritis ◽

Signaling Pathway ◽

Small Rnas ◽

High Throughput Sequencing ◽

Target Genes ◽

Expression Profiles ◽

Mapk Signaling ◽

Pcr Analysis ◽

Clinical Indicators ◽

Qrt Pcr

Objective Lupus nephritis (LN) is a major end-organ complication of systemic lupus erythematosus (SLE), and the molecular mechanism of LN is not completely clear. Accumulating pieces of evidence indicate the potential vital role of tRNA-derived small RNAs (tsRNAs) in human diseases. Current study aimed to investigate the potential roles of tsRNAs in LN. Methods We herein employed high‐throughput sequencing to screen the expression profiles of tsRNAs in renal tissues of the LN and control groups. To validate the sequencing data, we performed quantitative real-time PCR (qRT-PCR) analysis. Correlational analysis of verified tsRNAs expression and clinical indicators was conducted using linear regression. The potential target genes were also predicted. The biological functions of tsRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results Our findings revealed that the expression profiles of tsRNAs were significantly altered in the kidney tissues from LN patients compared with control. Overall, 160 tsRNAs were significantly dysregulated in the LN group, of which 79 were upregulated, whereas 81 were downregulated. Subsequent qRT-PCR results confirmed the different expression of candidate tsRNAs. Correlation analysis results found that expression of verified tsRNAs were correlated to clinical indicators. The target prediction results revealed that verified tsRNAs might act on 712 target genes. Further bioinformatics analysis uncovered tsRNAs might participate in the pathogenesis of LN through several associated pathways, including cell adhesion molecules, MAPK signaling pathway, PI3K-Akt signaling pathway and B cell receptor signaling pathway. Conclusion This study provides a novel insight for studying the mechanism of LN.

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Discovery of genes associated with sulfate-reducing bacteria biofilm using text mining and biological network analysis

10.1109/bibm52615.2021.9669374 ◽

2021 ◽

Author(s):

Abhilash Kumar Tripathi ◽

Priya Saxena ◽

Payal Thakur ◽

Shailabh Rauniyar ◽

Vinoj Gopalakrishnan ◽

...

Keyword(s):

Network Analysis ◽

Text Mining ◽

Biological Network ◽

Sulfate Reducing Bacteria ◽

Sulfate Reducing ◽

Biological Network Analysis ◽

Reducing Bacteria

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Analysis of MicroRNA Transcriptomes Insights into the miR-148a-3p Inducer of Rumen Development in Goats

10.21203/rs.3.rs-40834/v1 ◽

2020 ◽

Author(s):

Tao Zhong ◽

Cheng Wang ◽

Jiangtao Hu ◽

Xiaoyong Chen ◽

Lili Niu ◽

...

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Genetic Regulation ◽

Mapk Signaling ◽

Regulation Mechanism ◽

Ras Signaling ◽

Genome Wide ◽

A Genome ◽

Differentially Expressed Mirnas ◽

And Function

Abstract Background: Rumen is an important digestive organ of ruminant. From fetal to adult stage, the morphology, structure and function of rumen have changed significantly. But the intrinsic genetic regulation is still limited. We previously reported a genome-wide expression profile of miRNAs in prenatal goat rumens. In the present study, we rejoined analyzed the transcriptomes of rumen miRNAs during prenatal (E60 and E135) and postnatal (D30 and D150) stages.Results: A total of 66 differentially expressed miRNAs (DEMs) were identified in the rumen tissues from D30 and D150 goats. Of these, 17 DEMs were consistently highly expressed in the rumens at the preweaning stages (E60, E135 and D30), while down-regulated at D150. Noteworthy, annotation analysis revealed that the target genes regulated by the DEMs were mainly enriched in MAPK signaling pathway, Jak-STAT signaling pathway and Ras signaling pathway. Interestingly, the expression of miR-148a-3p was significantly high in the embryonic stage and down-regulated at D150. The potential binding sites between miR-148a-3p and QKI were predicted by the TargetScan and verified by the dual luciferase report assay. The co-localization of miR-148a-3p and QKI was observed not in intestinal tracts but in rumen tissues by in situ hybridization. Moreover, the expression of miR-148a-3p in the epithelium was significantly higher than that in the other layers, suggesting that miR-148a-3p involve in the development of rumen epithelial cells by targeting QKI. Subsequently, miR-148a-3p inhibitor was found to induce the proliferation of GES-1 cells.Conclusions: Taken together, these results identified the DEMs involved in the development of rumen and provided an insight into the regulation mechanism of goat rumens during development.

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Biological Network Analysis

10.1016/c2018-0-01461-9 ◽

2020 ◽

Keyword(s):

Network Analysis ◽

Biological Network ◽

Biological Network Analysis

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Biological Network Analysis and Subnetwork Extraction Tool

2018 9th International Conference on Information, Intelligence, Systems and Applications (IISA) ◽

10.1109/iisa.2018.8633646 ◽

2018 ◽

Author(s):

Danielle M. Rodriguez ◽

Angelyn Lao ◽

Geoffrey A. Solano

Keyword(s):

Network Analysis ◽

Biological Network ◽

Biological Network Analysis

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Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1388-4 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 10

Author(s):

Shan Lei ◽

Zhiwei He ◽

Tengxiang Chen ◽

Xingjun Guo ◽

Zhirui Zeng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Mapk Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Migration And Invasion ◽

Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

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