Molecular therapy for malignant brain tumors using microRNAs of drug-resistant genes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293324
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kagawa University
• Principal Investigator: Tamiya Takashi 香川大学, 医学部, 教授 (50252953)
• Co-Investigator(Kenkyū-buntansha): 三宅 啓介 香川大学, 医学部附属病院, 講師 (00398033) ; 岡田 真樹 香川大学, 医学部附属病院, 助教 (40457346) ; 小川 大輔 香川大学, 医学部附属病院, 助教 (70524057) ; 河井 信行 香川大学, 医学部, 准教授 (40294756)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬剤耐性遺伝子 / MGMT / MicroRNA / 脳腫瘍

Outline of Final Research Achievements

It is well known that O6-methylguanine-DNA methyltransferase (MGMT) is related to resistance of aggressive brain tumor glioblastoma (GBM) to DNA alkylating agent Temozolomide (TMZ) therapy. In this study, we searched for microRNA that modulate MGMT expression and give better sensitivity to TMZ. One out of 6 microRNAs (miR-655) down regulated more than 40% MGMT mRNA and protein level in both T98G glioma cell line and primary GBM cell line (GBM30). We will also show that microRNA expressing GBM30 transplanted in nude mice showed better survival with injection of TMZ in vivo. Thus, this endogenous mechanism of suppressing drug resistance gene MGMT will increase chemo-sensitivity to TMZ.This study will provide a new target to enhance efficacy of chemotherapy. In addition, The (pro) renin receptor ((P)RR) as a modular within Wnt receptor complex is essential for early CNS development by the activation of Wnt/β-catenin signaling pathway. Then we examined the role of (P)RR in gliomas.

Free Research Field

脳神経外科