MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma

Yujiro Nakano, Takanobu Yoshimoto, Ryo Watanabe, Masanori Murakami, Tatsuya Fukuda, Kazutaka Saito, Yasuhisa Fujii, Takumi Akashi, Toshihiro Tanaka, Tetsuya Yamada, Mitsuhide Naruse, Yoshihiro Ogawa

Research output: Contribution to journalArticle

Abstract

Objective: The pathophysiology of aldosterone-producing adenomas (APAs) has been intensively investigated using genetic and epigenetic approaches. However, the role of miRNAs in APA is not fully understood. The present study profiled miRNAs in APAs as an exploratory approach to elucidate their pathophysiological roles in APAs. Design: Tissues of APAs and other adrenocortical adenomas were obtained from patients who underwent adrenalectomy. Methods: Candidate miRNAs differentially detected from samples were exam ined by whole miRNA sequencing. The expression of candidate miRNAs in APA tissues were further vali dated by real-time quantitative polymerase chain reaction (qPCR). Further, differential miRNA expression between APAs with and without KCNJ5 somatic mutations was examined. Prediction of miRNA target genes was performed by bioinformatics analysis. For specific miRNAs, correlation analysis between the levels of their target genes and CYP11B2 was analyzed in APA tissues. Results: Our study determined differential expression of six miRNAs in A PA or APA with KCNJ5 mutations. We further demonstrated that miR299 levels were negatively correlated with mRNA levels of CACNB2, which encodes the beta-subunit of the L-type calcium channel. Additionally, we found s ignificant correlations among miR299, CACNB2, and CYP11B2 levels in APA tissues. Conclusions: Our study suggests the possible pathophysiological involvement of specific miRNAs in calcium signaling and aldosterone hypersecretion in APAs. Further studies, including in vitro analyses, are required to clarify these findings.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalEuropean Journal of Endocrinology
Volume181
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Cytochrome P-450 CYP11B2
Aldosterone
Adenoma
MicroRNAs
Adrenocortical Adenoma
L-Type Calcium Channels
Mutation
Calcium Signaling
Adrenalectomy
Computational Biology
Epigenomics
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma. / Nakano, Yujiro; Yoshimoto, Takanobu; Watanabe, Ryo; Murakami, Masanori; Fukuda, Tatsuya; Saito, Kazutaka; Fujii, Yasuhisa; Akashi, Takumi; Tanaka, Toshihiro; Yamada, Tetsuya; Naruse, Mitsuhide; Ogawa, Yoshihiro.

In: European Journal of Endocrinology, Vol. 181, No. 1, 01.01.2019, p. 69-78.

Research output: Contribution to journalArticle

Nakano, Y, Yoshimoto, T, Watanabe, R, Murakami, M, Fukuda, T, Saito, K, Fujii, Y, Akashi, T, Tanaka, T, Yamada, T, Naruse, M & Ogawa, Y 2019, 'MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma', European Journal of Endocrinology, vol. 181, no. 1, pp. 69-78. https://doi.org/10.1530/EJE-18-0882
Nakano Y, Yoshimoto T, Watanabe R, Murakami M, Fukuda T, Saito K et al. MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma. European Journal of Endocrinology. 2019 Jan 1;181(1):69-78. https://doi.org/10.1530/EJE-18-0882
Nakano, Yujiro ; Yoshimoto, Takanobu ; Watanabe, Ryo ; Murakami, Masanori ; Fukuda, Tatsuya ; Saito, Kazutaka ; Fujii, Yasuhisa ; Akashi, Takumi ; Tanaka, Toshihiro ; Yamada, Tetsuya ; Naruse, Mitsuhide ; Ogawa, Yoshihiro. / MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma. In: European Journal of Endocrinology. 2019 ; Vol. 181, No. 1. pp. 69-78.
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abstract = "Objective: The pathophysiology of aldosterone-producing adenomas (APAs) has been intensively investigated using genetic and epigenetic approaches. However, the role of miRNAs in APA is not fully understood. The present study profiled miRNAs in APAs as an exploratory approach to elucidate their pathophysiological roles in APAs. Design: Tissues of APAs and other adrenocortical adenomas were obtained from patients who underwent adrenalectomy. Methods: Candidate miRNAs differentially detected from samples were exam ined by whole miRNA sequencing. The expression of candidate miRNAs in APA tissues were further vali dated by real-time quantitative polymerase chain reaction (qPCR). Further, differential miRNA expression between APAs with and without KCNJ5 somatic mutations was examined. Prediction of miRNA target genes was performed by bioinformatics analysis. For specific miRNAs, correlation analysis between the levels of their target genes and CYP11B2 was analyzed in APA tissues. Results: Our study determined differential expression of six miRNAs in A PA or APA with KCNJ5 mutations. We further demonstrated that miR299 levels were negatively correlated with mRNA levels of CACNB2, which encodes the beta-subunit of the L-type calcium channel. Additionally, we found s ignificant correlations among miR299, CACNB2, and CYP11B2 levels in APA tissues. Conclusions: Our study suggests the possible pathophysiological involvement of specific miRNAs in calcium signaling and aldosterone hypersecretion in APAs. Further studies, including in vitro analyses, are required to clarify these findings.",
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AU - Fukuda, Tatsuya

AU - Saito, Kazutaka

AU - Fujii, Yasuhisa

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