Hesperidin administration suppresses the proliferation of lung cancer cells by promoting apoptosis via targeting the miR132/ZEB2 signalling pathway.
Int J Mol Med
; 46(6): 2069-2077, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33125117
ABSTRACT
This aim of the present study was to identify the relationship between hesperidin and microRNA (miR)132, and to study the role of hesperidin and miR132 in the pathogenesis of nonsmall cell lung cancer (NSCLC). Computational analysis and luciferase assays were performed to identify the target of miR132. Subsequently, reverse transcriptionquantitative PCR and western blot assays were used to detect the effect of miR132 and hesperidin on the expression of haematological and neurological expressed 1 (HN1) and zinc finger Ebox binding homeobox 2 (ZEB2). Finally, MTT assays and flow cytometry analysis were used to investigate the effect of hesperidin on cell proliferation and apoptosis. ZEB2 was identified as a target gene of miR132, and transfection with miR132 mimic reduced the luciferase activity of the wildtype ZEB2 3'untranslated region (3'UTR) but not that of the mutant ZEB2 3'UTR. By contrast, neither transfection with miR132 mimic nor hesperidin treatment affected HN1 expression. Furthermore, hesperidin evidently inhibited cell proliferation and promoted apoptosis in a dosedependent manner. Furthermore, the tumour volume in rats transplanted with NSCLC cells and treated with hesperidin was notably smaller compared with that in rats transplanted with NSCLC cells alone, while treatment with hesperidin significantly reduced the colony formation efficiency of NSCLC cells by increasing miR132 expression and decreasing ZEB2 expression. To the best of our knowledge, the present study demonstrated for the first time that the administration of hesperidin decreased the expression of ZEB2 by upregulating the expression of miR132, which in turn promoted apoptosis and inhibited the proliferation of NSCLC cells.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Apoptose
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MicroRNAs
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Homeobox 2 de Ligação a E-box com Dedos de Zinco
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Hesperidina
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Mol Med
Ano de publicação:
2020
Tipo de documento:
Article