Identification of novel therapeutic targets on alternative pre-mRNA splicing in digestive malignancy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: MIURA Koh 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (40282074)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 消化器癌 / 選択的pre-mRNAスプライシング / 治療標的 / 新規治療法 / 浸潤転移 / 発がん / 大腸癌

Outline of Final Research Achievements

Pyruvate kinase gene, which codes an enzyme essential for glycolytic pathway, has four isoforms of transcripts: L, R, M1 and M2. We especially focused on the M2 isoform and analyzed its expression levels in cancerous and corresponding normal tissues from gastric cancer patients and normal tissues from healthy individuals. The analysis revealed that the M2 isoform is highly expressed in cancer and normal tissues from gastric cancer patients. Along with in vivo experiments, the M2 isoform was shown to be important in development of gastric cancer (Shiroki T, et al. Cancer Sci. 2017; 108:931-940). We are also analyzing alternative pre-mRNA splicing of dihydropyrimidine dehydrogenase gene, which codes a catabolizing enzyme of 5-FU, under collaboration with Department of Surgery, Tohoku University. We found serpini1 gene has an important role in epithelial-to-mesenchymal transition in colorectal cancer, and we are exploring functions of the splice variants located in the 5'-UTR region.

Free Research Field

消化器癌