MiR-141-3p is upregulated in esophageal squamous cell carcinoma and targets pleckstrin homology domain leucine-rich repeat protein phosphatase-2, a negative regulator of the PI3K/AKT pathway

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19912
• 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, 大学院医学研究科, 研究生 (90552662)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: PI3K / AKT / マイクロRNA / miR-141

Outline of Final Research Achievements

The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is frequently activated in various human cancers and plays essential roles in their development and progression.
The miRNA microarray analysis revealed that miR-31-5p, miR-141-3p, miR-200b-3p, miR-200c-3p, and miR-205-5p were expressed at higher levels in the ESCC cell lines than the normal esophageal epithelial cell line. Bioinformatical analyses of mRNA microarray data identified several AKT/PI3K pathway-related genes as candidate targets of these miRNAs, which include tumor suppressors such as DNA-damage-inducible transcript 4 and pleckstrin homology domain leucine-rich repeat protein phosphatase-2 (PHLPP2). To validate the targets of relevant miRNAs experimentally, synthetic mimics of the miRNAs were transfected into the esophageal epithelial cell line.
Here,we report that miR-141-3p suppress the expression of PHLPP2, a negative regulators of the AKT/PI3K pathway, as a target in ESCC.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

食道扁平上皮癌とマイクロRNAの関連を調べたことで、今後の分子標的治療などへの可能性を広げることができた。