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ID 50710
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Author
Tanaka, Norimitsu
Kubo, Takafumi
Maki, Yuho
Muraoka, Takayuki
Furukawa, Masashi
Ueno, Tsuyoshi
Aoe, Keisuke
Abstract
Small-cell lung cancer (SCLC) is an aggressive tumor with a dismal prognosis among primary lung cancers. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family is comprised of tumor-suppressive miRNAs, and its reduced expression by methylation has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the alteration and tumor-suppressive impact of miR-34s in SCLC. The methylation of miR-34a and miR-34b/c was observed in 4 (36%) and 7 (64%) of 11 SCLC cell lines, respectively. Among the 27 SCLC clinical specimens, miR-34a and miR-34b/c were methylated in 4(15%) and 18 (67%), respectively. In contrast, 13 (28%) miR-34a methylated cases and 12 (26%) miR-34b/c methylated cases were found in 47 NSCLC primary tumors. The frequency of miR-34b/c methylation was significantly higher in SCLC than in NSCLC (p < 0.001). The expressions of miR-34s were reduced in methylated cell lines and tumors and restored after 5-aza-2'-deoxycytidine treatment, indicating that methylation was responsible for the reduced expression of miR-34s. Because the frequency of methylation was higher in miR-34b/c, we focused on miR-34b/c for a functional analysis. We examined the effect of miR-34b/c introduction on cell proliferation, migration and invasion. The transfection of miR-34b/c to two SCLC cell lines (H1048 and SBC5) resulted in the significant inhibition of cell growth, migration, and invasion, compared with control transfectants. Our results indicate that the aberrant methylation of miR-34b/c plays an important role in the pathogenesis of SCLC, implying that miR-34b/c may be a useful therapeutic target for SCLC.
Keywords
Methylation
MicroRNA
MicroRNA-34b/c
Small cell lung cancer
Non-small cell lung cancer
p53
Published Date
2012-04
Publication Title
Lung Cancer
Volume
volume76
Issue
issue1
Publisher
Elsevier Ireland Ltd.
Start Page
32
End Page
38
ISSN
0169-5002
NCID
AA10785743
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.lungcan.2011.10.002
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/50698
language
英語
Copyright Holders
(C) 2011 Elsevier Ireland Ltd. All rights reserved.
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Refereed
True
DOI
Web of Sience KeyUT