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ID 109400
タイトル別表記
口腔癌の増殖・転移に及ぼすmiR-518c-5pの関与
Role of miR-518c-5p in Oral Cancer
著者
木内, 誠 徳島大学大学院口腔科学教育部(口腔科学専攻)
キーワード
miRNA
CXCR4
oral cancer
metastasis
資料タイプ
学位論文
抄録
We have previously demonstrated that a stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral cancer. Recently, small non coding RNAs, microRNAs (miRNAs) have been shown to be involved in the metastatic process of several types of cancers. However, the miRNAs that contribute to metastases induced by the SDF-1/CXCR4 system in oral cancer are largely unknown. In this study, we examined the metastasis-related miRNAs induced by the SDF-1/CXCR4 system using B88-SDF-1 oral cancer cells, which exhibit functional CXCR4 and distant metastatic potential in vivo. Through miRNA microarray analysis, we identified the upregulation of miR-518c-5p in B88- SDF-1 cells, and confirmed the induction by real-time PCR analysis. Although an LNA-based miR-518c-5p inhibitor did not affect cell growth of B88-SDF-1 cells, it did significantly inhibit the migration of the cells. Next, we transfected a miR-518c expression vector into parental B88 cells and CAL27 oral cancer cells and isolated stable transfectants, B88-518c and CAL27-518c cells, respectively. The anchorage-dependent and -independent growth of miR-518c transfectants was significantly enhanced compared with the growth of mock cells. Moreover, we detected the enhanced migration of these cells. The LNA-based miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of miR-518c transfectants, indicating that these phenomena were mainly dependent on the expression of miR-518c-5p. Next, we examined the function of miR-518c-5p in vivo. miR-518c transfectants or mock transfectants were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with the miR-518c transfectants. These results indicated that miR-518c-5p regulates the growth and metastasis of oral cancer as a downstream target of the SDF-1/CXCR4 system.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
9
12
開始ページ
e115936
発行日
2014-12-23
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201505291004.pdf
審査要旨 : LID201505291005.pdf
論文本文 : LID201505291006.pdf
本論文は, 著者Makoto Kinouchiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: 2014 Kinouchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2811号
学位記番号
甲口第393号
学位授与年月日
2015-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系
病院