TY - JOUR
T1 - MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells
AU - Nishida, Naohiro
AU - Yamashita, Shinya
AU - Mimori, Koshi
AU - Sudo, Tomoya
AU - Tanaka, Fumiaki
AU - Shibata, Kohei
AU - Yamamoto, Hirofumi
AU - Ishii, Hideshi
AU - Doki, Yuichiro
AU - Mori, Masaki
N1 - Funding Information:
ACKNOWLEDGMENT The authors thank T. Shimooka, K. Og-ata, M. Kasagi, and T. Kawano for their excellent technical assistance. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency (JST); Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research: 21679006, 20390360, 20590313, 20591547, 21591644, 21592014, 20790960, 21791297, 21229015, 20659209 and 20012039; New Energy and Industrial Technology Development Organization) (NEDO) Technological Development for Chromosome Analysis; the Ministry of Education, Culture, Sports, Science and Technology of Japan for Scientific Research on Priority Areas, Cancer Translational Research Project, Japan.
PY - 2012/9
Y1 - 2012/9
N2 - 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 chemotherapyinduced 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 proapoptotic 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.
AB - 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 chemotherapyinduced 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 proapoptotic 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.
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U2 - 10.1245/s10434-012-2246-1
DO - 10.1245/s10434-012-2246-1
M3 - Article
C2 - 22322955
AN - SCOPUS:84867397137
SN - 1068-9265
VL - 19
SP - 3065
EP - 3071
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 9
ER -
