Evaluation of Exosomal miRNA in Blood as a Potential Diagnostic Biomarker for Human Non-Small Cell Lung Cancer

Gao

et al. 2021

Front. Cell Dev. Biol.

BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.

Section: Discussionmentioning

confidence: 71%

Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

Gao

et al. 2021

Front. Cell Dev. Biol.

“…Additionally, miR-181b-3p was recently found as one of the miRNAs with potential in discriminating neck lymph node metastasis, suggesting that this miRNA has a potential as a prognostic biomarker (Liu et al , 2020). Lastly, miR-4687-5p was found to be upregulated in lung adenocarcinoma metastasis and considered to be among potential miRNA biomarkers for small cell lung cancer (Xu et al , 2020).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profile in patients with cystic echinococcosis and identification of possible cellular pathways

et al. 2021

Cystic echinococcosis (CE) is a neglected tropical disease, caused by metacestode (larval) form of the Echinococcus granulosus sensu lato (sl) in humans. MicroRNAs (miRNAs) are small, stable, tissue-specific RNA molecules encoded by the genome that are not translated into proteins. Circulating miRNA expression profiles vary in health and disease. The aim of this study is to determine the altered cellular pathways in CE by comparing the miRNA profiles of controls and CE patients with active or inactive cysts. Following abdominal ultrasonography (US) examination, 20 patients diagnosed with active CE (CE1, CE2, CE3a and CE3b) or inactive CE (CE4 and CE5) and three healthy controls were included in the study. The expression profiles of 372 biologically relevant human miRNAs were investigated in serum samples from CE patients and healthy controls with miScript miRNA HC PCR Array. Compared with the control group, expression of 6 miRNAs (hsa-miR-4659a-5p, hsa-miR-4518, hsa-miR-3977, hsa-miR-4692, hsa-miR-181b-3p, hsa-miR-4491) and one miRNA (hsa-miR-4687-5p) were found to be downregulated in CE patients with active and inactive cysts, respectively (p < 0.05). For downregulated miRNAs in this study, predicted targets were found to be associated mainly with cell proliferation, apoptosis, cell-cell interactions and cell cycle regulation. Further studies in this direction may elucidate the pathogenesis of human CE and the relationship between CE and other pathologies.

“…Increased understanding of exosome biogenesis, structure, and function would enhance the performance of biomarkers in various kinds of disease diagnosis, prognosis, and surveillance. 267 …”

Section: Exosomes As Diagnostic Markersmentioning

confidence: 99%

A Comprehensive Review on Factors Influences Biogenesis, Functions, Therapeutic and Clinical Implications of Exosomes

Gurunathan¹,

Kang²,

Kim³

2021

IJN

198

157

Exosomes are nanoscale-sized membrane vesicles secreted by almost all cell types into the extracellular environment upon fusion of multivesicular bodies and plasma membrane. Biogenesis of exosomes is a protein quality control mechanism, and once released, exosomes transmit signals to other cells. The applications of exosomes have increased immensely in biomedical fields owing to their cell-specific cargos that facilitate intercellular communications with neighboring cells through the transfer of biologically active compounds. The diverse constituents of exosomes reflect their cell of origin and their detection in biological fluids represents a diagnostic marker for various diseases. Exosome research is expanding rapidly due to the potential for clinical application to therapeutics and diagnosis. However, several aspects of exosome biology remain elusive. To discover the use of exosomes in the biomedical applications, we must better understand the basic molecular mechanisms underlying their biogenesis and function. In this comprehensive review, we describe factors involved in exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research, and discuss future perspectives.