Crosstalk between microRNA and epigenome for cisplatin resistance in bladder cancer.

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16701
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Tetsuya Shindo 札幌医科大学, 医学部, 助教 (80749292)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 膀胱癌 / 抗癌剤耐性 / マイクロRNA / エピゲノム

Outline of Final Research Achievements

In general, metastatic bladder cancer often treated by cisplatin based systemic chemotherapy. However, prognosis of the disease is reported around a year. In previous reports, microRNA reported that it related to chemoresistance in several cancer. To unveil the mechanism of cispatin resistance in bladder cancer, we focused on microRNA 200b. According to our experiments, microRNA200b was extremely surpressed in cisplatin resistance bladder cancer cell line. Moreover, the microRNA was regulated by epigenome such as methylation. In the down stream of the microRNA several gene such as IGFBP3, ICAM1, TNFSF10 and histone coding gene were regulated. From our results, microRNA 200b may be the new strategy to overome chemoresistance in metastatic bladder cancer.

Free Research Field

膀胱癌

Academic Significance and Societal Importance of the Research Achievements

本邦の高齢化に伴い、膀胱癌など尿路上皮癌の患者は泌尿器科癌症例の多くを占めており、その治療は重要な意味を持つに至っている。通常転移を伴う膀胱癌においてはシスプラチンという抗癌剤を中心として治療を行う。一般に70％程度の症例では一時的に奏功するが、癌細胞が抗癌剤に対する耐性を獲得し病勢が悪化することが多い。膀胱癌が抗癌剤に対する耐性を獲得する機序としてマイクロRNAの関与が報告されており、我々は抗癌剤耐性化した膀胱癌細胞株を用いてシスプラチン耐性化にかかわるマイクロRNAを同定した。さらに本マイクロRNAの調整にかかわるエピゲノム機構を検討し耐性化機序の一端を明らかにすることができた。