Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA.

Abstract:

:Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-β, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-κB, p53, HIF-1α, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.

journal_name

Neoplasma

journal_title

Neoplasma

authors

Dai N,Zhong ZY,Cun YP,Qing Y,Chen Ch,Jiang P,Li MX,Wang D

doi

10.4149/neo_2013_050

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

384-94

issue

4

eissn

0028-2685

issn

1338-4317

journal_volume

60

pub_type

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