How do potassium ions regulate the formation for non-canonical structures of nucleic acids and tumor progressions?

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19152
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Konan University
• Principal Investigator: Naoki Sugimoto 甲南大学, 先端生命工学研究所, 教授 (60206430)
• Co-Investigator(Kenkyū-buntansha): 建石 寿枝 甲南大学, 先端生命工学研究所, 講師 (20593495)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: がん細胞 / カリウムイオン / 非二重らせん構造 / 転写変異 / がん遺伝子 / 定量的解析

Outline of Final Research Achievements

In this study, we investigated physicochemically how changes of intracellular chemical environments influence G-quadruplex formation and transcription during tumor progression in vitro and in cells. In vitro, the stable G-quadruplex formation inhibits transcription in a solution containing 150 mM KCl (standard condition in cells). As K+ concentration decreases, which decreases G-quadruplex stability, transcript production from templates with G-quadruplex-forming potential sequences in c-myc gene increases. In normal cell, the trend in transcript productions was similar to that in experiments in vitro, that is, transcription efficiency inversely correlated with G-quadruplex stability. Interestingly, higher transcript levels were produced from templates with G-quadruplex-forming potential in the highly metastatic breast cancer cell than in the normal cell. Our results suggest that in normal cell, K+ ions attenuate the transcription of certain oncogenes by stabilizing G-quadruplexes.

Free Research Field

生命分子化学

Academic Significance and Societal Importance of the Research Achievements

DNAは塩基の並びによって遺伝情報を保持している。一方でDNAは標準的な二重らせん構造だけでなく、非二重らせん構造も形成するが、非二重らせん構造の細胞内における役割は未だ明らかでなかった。本研究では、塩基の並びが同じDNAでも、正常細胞では四重らせんを優先的に形成して、がんの進行を促す遺伝子発現を抑制する一方、悪性がん細胞では四重らせん構造が解離し、がん遺伝子の転写を活性化することを見出した。