The mechanism of KLF5 gene suppression and the relationship exploration between the suppression and cell differentiation

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16957
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: The Nippon Dental University
• Principal Investigator: Mihara Nozomi 日本歯科大学, 生命歯学部, 講師 (00803264)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 口腔癌 / KLF5 / 細胞分化

Outline of Final Research Achievements

KLF5 is an important transcription factor for inhibition of epithelial cell differentiation and involved in cancer progression. However, the association of KLF5 expression regulatory mechanism with cell differentiation remains largely unknown. We previously demonstrated that the minimal essential region (MER) required for KLF5 basal expression and Sp3 binding to the MER was essential to the expression.
In this study, we identified CREB-mediated interaction between the MER and a silencer region of KLF5 located upstream the MER. CREB mediated the MER-the silencer region interaction could complex with the MER binding factor(s) other than Sp3. Calcium-induced keratinocyte differentiation altered the expression of KLF5 and CREB, suggesting that intracellular calcium concentration may be involved in the regulation of the expressions.

Free Research Field

細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

癌はDNA-based diseaseであり、癌発生の要因は遺伝子変異だけではなく、他の要因による影響を受けて複雑に絡み合っている。癌の発生や進行に関わる遺伝子の促進的な発現制御機構については多くの報告がある中、抑制的な発現制御機構についての報告は極めて少ない。本研究成果は、癌の悪性形質獲得に関わるKLF5遺伝子の全体的な発現制御機構の解明に繋がり、癌進行における新たな分子学的背景を明示し、新規の癌治療法が必要な疾患に対する社会的ニーズに大いに貢献すると考えられる。