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Cancer. 2012 Jul 1;118(13):3365-76. doi: 10.1002/cncr.26560. Epub 2011 Dec 2.

MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3.

Author information

1
Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood.

METHODS:

We detected miRNA-200b (miR-200b) expression in different lung adenocarcinoma cell lines and then focused on its roles in regulation of docetaxel chemoresistance. We also identified E2F3 as a novel target of miR-200b.

RESULTS:

Based on miRNA microarray data, miR-200b was identified as the most down-regulated miRNA in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-200b expression reversed docetaxel chemoresistance of lung adenocarcinoma cells through cell proliferation inhibition, apoptosis enhancement, and G(2) /M cell cycle arrest. In a nude mouse xenograft model, up-regulation of miR-200b significantly enhanced response of SPC-A1/DTX cells to docetaxel. Luciferase reporters containing the 3' untranslated region sequence of E2F3 messenger RNA were used to demonstrate that miR-200b could directly target E2F3. Small interfering RNA-mediated E2F3 knockdown revealed similar effects as that of ectopic miR-200b expression. Decreased miR-200b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with docetaxel-based chemotherapy and was proved to be correlated with high expression of E2F3, decreased sensitivity to docetaxel, and poor prognosis.

CONCLUSIONS:

Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel.

PMID:
22139708
DOI:
10.1002/cncr.26560
[Indexed for MEDLINE]
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