TY - JOUR
T1 - MiRNA299 involvement in CYP11B2 expression in aldosterone-producing adenoma
AU - Nakano, Yujiro
AU - Yoshimoto, Takanobu
AU - Watanabe, Ryo
AU - Murakami, Masanori
AU - Fukuda, Tatsuya
AU - Saito, Kazutaka
AU - Fujii, Yasuhisa
AU - Akashi, Takumi
AU - Tanaka, Toshihiro
AU - Yamada, Tetsuya
AU - Naruse, Mitsuhide
AU - Ogawa, Yoshihiro
N1 - Funding Information:
and Development (AMED) (grant number JP17ek0109122, JP18ek0109352) and Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (grant number T Y, 16K08962, M M, 16K19392).
Funding Information:
This work was supported by the Japan Primary Aldosteronism Study (JPAS) supported by a Research Grant from the Japan Agency for Medical Research
Publisher Copyright:
© 2019 European Society of Endocrinology.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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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U2 - 10.1530/EJE-18-0882
DO - 10.1530/EJE-18-0882
M3 - Article
C2 - 31096184
AN - SCOPUS:85067906123
VL - 181
SP - 69
EP - 78
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
SN - 0804-4643
IS - 1
ER -