Journal
ANNALS OF SURGICAL ONCOLOGY
Volume 19, Issue 9, Pages 3065-3071Publisher
SPRINGER
DOI: 10.1245/s10434-012-2246-1
Keywords
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Funding
- CREST, Japan Science and Technology Agency (JST)
- Japan Society for the Promotion of Science (JSPS) [21679006, 20390360, 20590313, 20591547, 21591644, 21592014, 20790960, 21791297, 21229015, 20659209, 20012039]
- New Energy and Industrial Technology Development Organization) (NEDO) Technological Development for Chromosome Analysis
- Ministry of Education, Culture, Sports, Science and Technology of Japan for Scientific Research on Priority Areas, Cancer Translational Research Project, Japan
- Grants-in-Aid for Scientific Research [20590313, 22501015, 21592014, 23591937, 23390199, 21591644] Funding Source: KAKEN
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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. 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. 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. 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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