Human basonuclin 2 up-regulates a cascade set of interferon-stimulated genes with anti-cancerous properties in a lung cancer modelReportar como inadecuado




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Cancer Cell International

, 17:18

First Online: 06 February 2017Received: 03 September 2016Accepted: 01 February 2017

Abstract

BackgroundHuman basonuclin 2 BNC2 acts as a tumor suppressor in multiple cancers in an as yet unidentified manner. The role and expression of the BNC2 gene in lung cancer has not yet been investigated.

MethodsBNC2 expression was studied in the A549 and BEAS-2B cell lines, as well as in lung cancer tissue. Illumina array analysis and a viability assay were used to study the effects of transient transfection of BNC2 in A549 cells. Ingenuity pathway analysis and g:Profiler were applied to identify affected pathways and networks. RT-qPCR was used to validate the array results.

ResultsWe showed the reduced mRNA expression of BNC2 in non-small cell lung cancer tissue and lung cancer cell line A549 compared to non-cancerous lung tissue and BEAS-2B cells, respectively. Further array analysis demonstrated that the transfection of BNC2 into A549 cells resulted in the increased expression of 139 genes and the down-regulation of 13 genes. Pathway analysis revealed that half of the up-regulated genes were from the interferon-signal transducer and activator of transcription signaling pathways. The differential expression of selected sets of genes, including interferon-stimulated and tumor suppressor genes of the XAF1 and OAS families, was confirmed by RT-qPCR. In addition, we showed that the over-expression of BNC2 inhibited the proliferation of A549 cells.

ConclusionOur data suggest that human BNC2 is an activator of a subset of IFN-regulated genes and might thereby act as a tumor suppressor.

KeywordsBNC2 Type I IFN XAF1 OAS family Lung cancer AbbreviationsBNC2basonuclin 2

A549adenocarcinomic human alveolar basal epithelial cell line

BEAS-2Bhuman normal lung epithelial cell line

NSCLCnon-small cell lung cancer

IFNinterferon

XAF1XIAP associated factor-1

OAS2,5-oligoadenylate synthetase

CTLA-4cytotoxic T-lymphocyte antigen-4

PD-1programmed cell death-1 protein receptor

IRFinterferon regulatory factor

ISGinterferon stimulated gene

MXmyxovirus resistance protein

DAPKdeath activating protein kinase

HaCaTaneuploid immortal keratinocyte cell line from adult human skin

HeLacervical cancer cell line

HEK293human embryonic kidney cell line

SCCsquamous cell carcinoma

ESDesterase D

FDRfalse discovery rate

IFITMinterferon-induced transmembrane protein

NLSnuclear localization signal

NF-κBnuclear factor kappa-light-chain-enhancer of activated B cells

IFITinterferon Induced Protein with tetratricopeptide repeats

XIAPX-linked inhibitor of apoptosis protein activator

ATPadenosine triphosphate

PKRprotein kinase R

Electronic supplementary materialThe online version of this article doi:10.1186-s12935-017-0394-x contains supplementary material, which is available to authorized users.

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Autor: Egon Urgard - Anu Reigo - Eva Reinmaa - Ana Rebane - Andres Metspalu

Fuente: https://link.springer.com/article/10.1186/s12935-017-0394-x



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