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Title 

Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells

 

miR-196b의 표적유전자 homeoboxA9는 비소세포 폐암에서 NF-KB 활성을 통해서 악성 조절

Authors 

S L YuDong Chul LeeH A SohnS Y LeeH S JeonJ H LeeC G ParkH Y LeeYoung Il YeomJ W SonY S YoonJ Kang

Publisher 

Wiley-Blackwell

Issue Date 

2016

Citation 

Molecular Carcinogenesis, vol. 55, no. 12, pp. 1915-1926

Keywords 

EMTHOXA9miR-196bNF-κBNSCLC

Abstract 

MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor?kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents.

ISSN 

0899-1987

Link 

http://dx.doi.org/10.1002/mc.22439

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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