MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells

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

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3065-3071
Number of pages7
JournalAnnals of Surgical Oncology
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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