Micro RNA expression in serrated pathway and its association with a potential target therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Dokkyo Medical University
• Principal Investigator: MITOMI Hiroyuki 獨協医科大学, 医学部, 教授 (90181940)
• Co-Investigator(Kenkyū-buntansha): SAITO Tsuyoshi 順天堂大学, 医学部人体病理病態学講座, 准教授 (80439736)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: マイクロRNA / 広基性鋸歯状腺腫/ポリープ / 鋸歯状発癌経路 / 大腸ポリープ / 遺伝子メチル化

Outline of Final Research Achievements

Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated pathway leading to colorectal cancer development. To clarify WNT signaling activation and expression of microRNAs (20a/21/93/181b) in this pathway, we performed β-catenin immunostaining and methylation specific PCR for AXIN2, MCC and secreted frizzled-related proteins in SSA/Ps, SSA/Ps with high-grade dysplasia (SSA/P+HGD) and SSA/Ps with submucosal carcinoma (SSA/P+SM-Ca). Nuclear β-catenin immunolabelings and the methylation of AXIN2 or MCC showed stepwise increment from SSA/Ps through SSA/P+HGD to SSA/P+SM-Ca. A stepwise increment of miR21 and a stepwise decrement of miR20a/93/181b expressions were seen in this sequence. There were significant correlations of those miR expressions with AXIN2 or MCC methylation in this pathway. Our results point toward a potential target therapy of those miRs and methylated genes such as RNA-interference drug or demethylase in malignant progression of SSA/P.

Free Research Field

医学歯学