MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions

Miki Ito, Kei Mitsuhashi, Hisayoshi Igarashi, Katsuhiko Nosho, Takafumi Naito, Shinji Yoshii, Hiroaki Takahashi, Masahiro Fujita, Yasutaka Sukawa, Eiichiro Yamamoto, Taiga Takahashi, Yasushi Adachi, Masanori Nojima, Yasushi Sasaki, Takashi Tokino, Yoshifumi Baba, Reo Maruyama, Hiromu Suzuki, Kohzoh Imai, Hiroyuki YamamotoYasuhisa Shinomura

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The CpG island methylator phenotype (CIMP) is a distinct form of epigenomic instability. Many CIMP-high colorectal cancers (CRCs) with BRAF mutation are considered to arise from serrated pathway. We recently reported that microRNA-31 (miR-31) is associated with BRAF mutation in colorectal tumors. Emerging new approaches have revealed gradual changes in BRAF mutation and CIMP-high throughout the colorectum in CRCs. Here, we attempted to identify a possible association between miR-31 and epigenetic features in serrated pathway, and hypothesized that miR-31 supports the colorectal continuum concept. We evaluated miR-31 expression, BRAF mutation and epigenetic features including CIMP status in 381 serrated lesions and 222 non-serrated adenomas and examined associations between them and tumor location (rectum; sigmoid, descending, transverse and ascending colon and cecum). A significant association was observed between high miR-31 expression and CIMPhigh status in serrated lesions with BRAF mutation (p=0.0001). In contrast, miR-31 was slightly but insignificantly associated with CIMP status in the cases with wild-type BRAF. miR-31 expression in sessile serrated adenomas (SSAs) with cytological dysplasia was higher than that in SSAs, whereas, no significant difference was observed between traditional serrated adenomas (TSAs) and TSAs with high-grade dysplasia. The frequency of miR-31, BRAF mutation CIMP-high and MLH1 methylation increased gradually from the rectum to cecum in serrated lesions. In conclusion, miR-31 expression was associated with CIMP-high status in serrated lesions with BRAF mutation. Our data also suggested that miR-31 plays an important role in SSA evolution and may be a molecule supporting the colorectal continuum.

Original languageEnglish
Pages (from-to)2507-2515
Number of pages9
JournalInternational Journal of Cancer
Volume135
Issue number11
DOIs
Publication statusPublished - 2014

Keywords

  • BRAF
  • CIMP
  • Colon
  • Serrated polyp
  • miR-31

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ito, M., Mitsuhashi, K., Igarashi, H., Nosho, K., Naito, T., Yoshii, S., Takahashi, H., Fujita, M., Sukawa, Y., Yamamoto, E., Takahashi, T., Adachi, Y., Nojima, M., Sasaki, Y., Tokino, T., Baba, Y., Maruyama, R., Suzuki, H., Imai, K., ... Shinomura, Y. (2014). MicroRNA-31 expression in relation to BRAF mutation, CpG island methylation and colorectal continuum in serrated lesions. International Journal of Cancer, 135(11), 2507-2515. https://doi.org/10.1002/ijc.28920