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ID 50710
フルテキストURL
著者
Tanaka, Norimitsu Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Toyooka, Shinichi Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Soh, Junichi Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Kubo, Takafumi Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Yamamoto, Hiromasa Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Maki, Yuho Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Muraoka, Takayuki Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Shien, Kazuhiko Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Furukawa, Masashi Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Ueno, Tsuyoshi Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Asano, Hiroaki Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Tsukuda, Kazunori Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
Aoe, Keisuke Natl Hosp Org Yamaguchi Ube Med Ctr, Dept Med Oncol
Miyoshi, Shinichiro Okayama Univ, Dept Canc & Thorac Surg, Grad Sch Med Dent & Pharmaceut Sci
抄録
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.
キーワード
Methylation
MicroRNA
MicroRNA-34b/c
Small cell lung cancer
Non-small cell lung cancer
p53
発行日
2012-04
出版物タイトル
Lung Cancer
76巻
1号
出版者
Elsevier Ireland Ltd.
開始ページ
32
終了ページ
38
ISSN
0169-5002
NCID
AA10785743
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.lungcan.2011.10.002
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/50698
言語
English
OAI-PMH Set
岡山大学
著作権者
(C) 2011 Elsevier Ireland Ltd. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT