Erschienen in:
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
verfasst von:
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
Erschienen in:
Annals of Surgical Oncology
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Ausgabe 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.