ID 112375
Title Alternative
microRNA-100/microRNA-125b発現の低下は大腸粘膜下層浸潤癌のリンパ節転移に関与する
Downregulation of microRNA-100/microRNA-125b
Author
Fujimoto, Akiko Tokushima University
Keywords
Cancer invasion
colorectal cancer with submucosal invasion
lymph node metastasis
miR-100
miR-125b
colorectal cancer
miRNA
Content Type
Thesis or Dissertation
Description
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real-time PCR identified mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 receptor (IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein (XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.
Journal Title
Cancer Science
ISSN
13497006
Publisher
Japanese Cancer Association|Wiley Publishing Asia Pty Ltd
Volume
108
Issue
3
Start Page
390
End Page
397
Published Date
2016-12-29
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201705191011.pdf
論文本文:k3025_fulltext.pdf
本論文は,著者Yasuteru Fujino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。
著者の申請により要約(2017-05-19公開)に替えて論文全文を公開(2018-06-14)
Rights
© 2016 The Authors Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.( https://creativecommons.org/licenses/by-nc/4.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3025号
Diploma Number
甲医第1329号
Granted Date
2017-03-21
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences