MiR-155 inhibits the sensitivity of lung cancer cells to cisplatin via negative regulation of Apaf-1 expression

MicroRNA-155 (miR-155) overexpression is often found in malignancies including lung cancer. The objective of this study is to verify the hypothesis, based on the results of bioinformatics analysis, that miR-155 modulates cellular apoptosis and DNA damage through the regulation of Apaf-1 and is thus...

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Vydáno v:	Cancer gene therapy Ročník 19; číslo 11; s. 773 - 778
Hlavní autoři:	Zang, Y-S, Zhong, Y-F, Fang, Z, Li, B, An, J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.11.2012 Nature Publishing Group
Témata:	631/337/384/331 631/67/1059/99 631/67/68 692/699/67/1612 Antineoplastic Agents - pharmacology Apaf-1 protein Apoptosis Apoptotic Protease-Activating Factor 1 - genetics Apoptotic Protease-Activating Factor 1 - metabolism Bioinformatics Biomedical and Life Sciences Biomedicine Care and treatment Caspase 9 - genetics Caspase 9 - metabolism Cell Line, Tumor Cellular signal transduction Cisplatin Cisplatin - pharmacology Comet Assay Control Deoxyribonucleic acid DNA DNA Damage Drug Resistance, Neoplasm - drug effects Gene Expression Gene Expression Regulation, Neoplastic Gene Silencing Gene Therapy Health aspects Humans Lung cancer Lung Neoplasms - metabolism Lung Neoplasms - pathology MicroRNAs - genetics MicroRNAs - metabolism miRNA mRNA original-article Physiological aspects RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - genetics RNA, Small Interfering - metabolism siRNA Transfection lung cancer apoptosis Apaf-1 cisplatin miR-155 DNA damage
ISSN:	0929-1903, 1476-5500, 1476-5500
On-line přístup:	Získat plný text
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Shrnutí:	MicroRNA-155 (miR-155) overexpression is often found in malignancies including lung cancer. The objective of this study is to verify the hypothesis, based on the results of bioinformatics analysis, that miR-155 modulates cellular apoptosis and DNA damage through the regulation of Apaf-1 and is thus involved in the development and progression of lung cancer. First, we measured the expression of miR-155 and the Apaf-1 protein in lung cancer tissues. The results showed that expression of miR-155 was significantly higher in lung cancer tissues than in paracancerous and normal tissues; whereas Apaf-1 expression was lower in the lung cancerous tissues. We then established miR-155-silenced and Apaf-1-overexpressed A549 cell lines by transfection with pMAGic2.0-BIC-siRNA and pcDNA3.1-Apaf-1, respectively. These cell lines were then treated with cisplatin, and apoptosis and DNA damage were assessed, with non-transfected A549 cells used as negative controls. The results showed that, relative to controls, the silencing of miR-155 resulted in elevated expression of the Apaf-1 protein, whereas Apaf-1 mRNA levels remained unchanged. Both the silencing of miR-155 and the overexpression Apaf-1 greatly increased the sensitivity of A549 cells to cisplatin treatment, as evidenced by elevated rates of apoptosis and DNA damage. Furthermore, dual-transfection of A549 cells with miR-155 siRNA and Apaf-1 siRNA resulted in the attenuation of apoptosis and DNA damage. In conclusion, the inhibition of miR-155 can enhance the sensitivity of A549 cells to cisplatin treatment by modulation of cellular apoptosis and DNA damage through an Apaf-1-mediated pathway.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0929-1903 1476-5500 1476-5500
DOI:	10.1038/cgt.2012.60