Effect of miR146a5p on tumor growth in NSCLC using chick chorioallantoic membrane assay and bioinformatics investigation.
Mol Med Rep
; 16(6): 8781-8792, 2017 Dec.
Article
en En
| MEDLINE
| ID: mdl-28990079
ABSTRACT
Our previous study demonstrated that the expression of miR146a5p was downregulated in nonsmall cell lung cancer (NSCLC) tissue, which affected the progression and prognosis of patients with NSCLC. Thus, the present study was conducted to investigate the functional mechanism of miR146a5p in tumorigenesis and angiogenesis in NSCLC. Following the construction of a H460 NSCLC cell line in which miR146a5p was overexpressed via lentivirus transduction, the NSCLC chick embryo chorioallantoic membrane (CAM) model was established by transplanting miR146a5poverexpressing NSCLC cells into the CAM. Then, the size of the neoplasms within the CAM was measured, the vessel ratio was calculated, and the cellular morphology, metastasis and inflammation of tumor cell was observed using hematoxylin and eosin staining. The target genes of miR146a5p were predicted by 12 online software programs; these genes were then subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway annotations using the Database for Annotation, Visualization and Integrated Discovery 6.7 as well as constructed into a protein interaction network using proteinprotein interaction from Search Tool for the Retrieval of Interacting Genes/Proteins. The xenograft tumor size and angiogenesis conditions of the miR146a5poverexpressing group (volume 6.340±0.066 mm3, vessel ratio 9.326±0.083) was obviously restricted (P<0.001) when compared with the low expression group (volume 30.13±0.06 mm3, vessel ratio 16.94±0.11). In addition, marked necrosis along with inflammatory cell infiltration was observed with the HEstained slices from the miR146a5p low expression group. Regarding the results of the target gene prediction, cancer and tolllike receptor signaling were the two most significant pathways represented among the target genes, while JUN, EGFR and RAC1 were the most relevant proteins among the selected potential targets of miR146a5p. In a CAM xenograft tumor model, overexpression of miR146a5p inhibited the tumorigenesis and angiogenesis of an NSCLC cell line. miR146a5p may act as a tumor suppressor gene in NSCLC and have moderate prognostic value in lung cancer.
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Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Biología Computacional
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MicroARNs
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Neoplasias Pulmonares
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Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Med Rep
Año:
2017
Tipo del documento:
Article