Comprehensive analysis of PIK3CA-Akt pathway and miRNAs

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791449
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nippon Medical School
• Principal Investigator: AKAGI ICHIRO 日本医科大学, 医学部, 助教 (90552662)
• Co-Investigator(Renkei-kenkyūsha): ISHIBASHI Osamu 大阪府立大学, 生命環境学研究科, 准教授 (70293214)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: PI3K / Akt / miR-141 / miR-200 / DDIT4 / PHLPP2

Outline of Final Research Achievements

We focused on PI3K-AKT pathway and investigated comprehensively mRNA and miRNA expression in normal and tumorous human esophageal squamous cell lines. Using integrated statistical analyses, we identified miR-141, miR-200b, miR-200c, and miR-205 as highly up-regulated onco-miRs in esophageal squamous cell carcinoma (ESCC). According to the computational program TargetScan and our microarray-based comprehensive gene expression analysis, we detected DNA damage-inducible transcript 4 protein (DDIT4) as a target of miR-200b and miR-200c and which was downregulated in ESCC. Also, we detected PH Domain Leucine-Rich Repeat-Containing Protein Phosphatase 2 (PHLPP2) as a target for miR-141 and which was downregulated in ESCC. As expected, the transfection of miR-141 mimic resulted in significant decrease of the expression of PHLPP2 in esophageal epithelial cell line. These results suggest that miR-141 is a negative regulator of PHLPP2 and promotes cell proliferation in ESCC.

Free Research Field

食道外科