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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Bibliographic Details
Published in:Cancer gene therapy Vol. 19; no. 11; pp. 773 - 778
Main Authors: Zang, Y-S, Zhong, Y-F, Fang, Z, Li, B, An, J
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.11.2012
Nature Publishing Group
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:0929-1903
1476-5500
1476-5500
DOI:10.1038/cgt.2012.60