Elucidating the significance of circular RNAs in steroid hormone-producing cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08922
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Fukuoka University
• Principal Investigator: Tanaka Tomoko 福岡大学, 医学部, 講師 (10380528)
• Co-Investigator(Kenkyū-buntansha): 大江 賢治 福岡大学, 薬学部, 教授 (30419527) ; 田邉 真紀人 福岡大学, 医学部, 准教授 (60707305)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 環状RNA / 副腎 / ステロイドホルモン / NR5A1

Outline of Final Research Achievements

Recently, sequence analysis of gene transcripts by next-generation sequencers has revealed the presence of functional RNAs with circular structures besides linear RNA. The nuclear receptor NR5A1 (also known as Ad4BP/SF-1) is an essential regulator of steroid hormone production and is present in the nuclei of the normal adrenal cortex and adrenal tumor cells. In adrenocortical carcinomas, the higher the expression of NR5A1, the worse the prognosis. We found a circular NR5A1 RNA (NR5A1 circRNA) not detected in adrenocortical carcinoma cell lines but only in the normal adrenal cortex. Circular RNAs are structurally stable molecules, making them a potential novel biomarker. The making process of NR5A1 circRNA and its function is still unknown. In this study, we analyzed the significance of cyclic RNAs in steroidogenesis, focusing on NR5A1 circRNA, and elucidated the mechanism of adrenal steroidogenesis regulated by functional circular RNAs.

Free Research Field

内分泌学　分子生物学

Academic Significance and Societal Importance of the Research Achievements

副腎皮質癌は希少な癌で難治性である。本邦における副腎偶発腫瘍3,678例中1.4%にみられ、5年生存率は35－50％と予後不良である 副腎皮質癌においては、NR5A1の発現量が多いほど、予後が悪い とされる。本研究の結果、環状RNAはNR5A1の発現調節に関与しており、副腎腫瘍と正常副腎では、NR5A1環状RNAに違いがあることが明らかになった。NR5A1環状RNAと副腎腫瘍の病態像について解析を進めることで副腎腫瘍の治療法の開発や機序の解明に役立つ。