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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2012

01-09-2012 | Translational Research and Biomarkers

MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells

Authors: Naohiro Nishida, MD, Shinya Yamashita, MD, Koshi Mimori, MD, PhD, Tomoya Sudo, MD, PhD, Fumiaki Tanaka, MD, PhD, Kohei Shibata, MD, PhD, Hirofumi Yamamoto, MD, PhD, Hideshi Ishii, MD, PhD, Yuichiro Doki, MD, PhD, Masaki Mori, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 9/2012

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Abstract

Purpose

Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.

Methods

Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.

Results

High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P = 0.0257) and poor prognosis (P = 0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.

Conclusions

MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.
Appendix
Available only for authorised users
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Metadata
Title
MicroRNA-10b is a Prognostic Indicator in Colorectal Cancer and Confers Resistance to the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cells
Authors
Naohiro Nishida, MD
Shinya Yamashita, MD
Koshi Mimori, MD, PhD
Tomoya Sudo, MD, PhD
Fumiaki Tanaka, MD, PhD
Kohei Shibata, MD, PhD
Hirofumi Yamamoto, MD, PhD
Hideshi Ishii, MD, PhD
Yuichiro Doki, MD, PhD
Masaki Mori, MD, PhD, FACS
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2246-1

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