Comprehensive analysis of epigenetic alteration and lncRNA involved to colon cancer development

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07977
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Niinuma Takeshi 札幌医科大学, 医学部, 助教 (60708113)
• Co-Investigator(Kenkyū-buntansha): 鈴木 拓 札幌医科大学, 医学部, 教授 (20381254)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 消化器がん / エピジェネティクス / noncoding RNA

Outline of Final Research Achievements

In this study, we analyzed the expression of lncRNA in gastrointestinal tumors by using publicly available TCGA database and compared that in normal tissues or tumors. We tested several methods to select the prospective lncRNA genes and analyzed the function of selected lncRNAs. Among them, we assessed the function of lncX gene. Depletion of lncX by using specific siRNA reduced cell viability and induced apoptosis in several cancer cells. To investigate the effects on gene expression profiles by knockdown of lncX, we performed gene expression microarray analysis. Accordingly, we found that a number of genes regulating cell cycle were significantly downregulated. We confirmed the reduction of AURKA, cyclin B1, and survivin. Then, we performed luciferase reporter assay by using promoter of AURKA gene. We assessed the effects of lncX with WT CED or Mut CED reporter. Consequently, results of reporter assay suggest that lncX is involve to the activation of cell cycle genes.

Free Research Field

消化器がん

Academic Significance and Societal Importance of the Research Achievements

本研究では消化管がんの増殖を抑制するノンコーディングRNA分子を発見しています。この分子を抑制することで腫瘍細胞の細胞死が誘導される事や、細胞分裂に関連する遺伝子群を制御していることが明らかとなりました。詳細なメカニズムについてはこれからさらに解析する必用がありますが、この分子は正常では発現が低いために、この分子を標的とする治療はがんに特異的なものになる可能性があると考えられます。