Omics analysis of APA with KCNJ5 mutation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22896
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Murakami Masanori 東京医科歯科大学, 東京医科歯科大学病院, 助教 (00740432)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 内分泌学 / 副腎腫瘍 / 原発性アルドステロン症 / 高血圧

Outline of Final Research Achievements

We conducted transcriptome analysis of aldosterone-producing adenoma and functional analysis of candidate genes using human adrenocortical carcinoma cell line. In this study, we found that one of the calcium channel gene, CACNB2, and aldosterone synthase gene, CYP11B2, showed positive correlation in mRNA expression. We also found that HPSE gene, which is involved with cleavage of heparan sulfate proteoglycans, was specifically expressed in APA with KCNJ5 mutation. Furthermore, our analysis suggested that both CACNB2 and HPSE genes were possibly regulated by miRNA in APA tissues.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

難治性高血圧の原因の一つであるアルドステロン産生腺腫(APA)は、原発性アルドステロン症の約30%を占めており、その発症メカニズムを明らかにすることは新規診断・治療法の開発につながる。本研究によってAPA発症に関与すると考えられる候補遺伝子を見出し、機能解析を開始することが出来た。候補遺伝子の制御にはmiRNAの関与も示唆されており、ホルモン分泌能と腫瘍化の両面を有する内分泌腫瘍研究に貴重な知見を与えたと言える。