The lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA network inhibits cardiomyocyte hypertrophy in hypertrophic obstructive cardiomyopathy.

IF 1.3 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedical Research-tokyo Pub Date : 2023-01-01 DOI:10.2220/biomedres.44.105

Bangrong Song, Wei Li, Xiaoyu Xu, Haiming Dang, Ran Dong

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引用次数: 1

Abstract

Hypertrophic obstructive cardiomyopathy (HOCM) is a well-recognized inherited cardiac disease. This study was conducted to explore the role of lncRNA ADAMTS9 antisense RNA 1 (ADAMTS9-AS1) in HOCM-induced cardiomyocyte hypertrophy. The serum of HOCM patients was collected. AC16 cells were treated with isoproterenol (ISO) and transfected with oe-ADAMTS9-AS1 vector, miR-185-5p mimic, and lysine acetyltransferase 7 (KAT7) specific small interfering RNA. lncRNA ADAMTS9-AS1, miR-185-5p, KAT7, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in the serum or cells were determine by qRT-PCR or Western blot assay. Cell surface area was observed by Texas Red-Phalloidin staining. Subcellular localization of lncRNA ADAMTS9-AS1 was tested by nuclear/cytoplasmic fractionation assay, with RNA pull-down and dual-luciferase assay to validate gene interactions. lncRNA ADAMTS9-AS1 was downregulated in the serum of HOCM patients and ISO-treated AC16 cells. lncRNA ADAMTS9-AS1 overexpression inhibited ISO-induced cardiomyocyte hypertrophy and reduced levels of ANP and BNP. lncRNA ADAMTS9- AS1 was located in cytoplasm and inhibited miR-185-5p expression through targeted binding. miR-185-5p bound to KAT7 3'UTR and inhibited KAT7 expression. miR-185-5p overexpression and KAT7 knockdown both neutralized the inhibitory role of lncRNA ADAMTS9-AS1 in cardiomyocyte hypertrophy. Overall, lncRNA ADAMTS9-AS competitively bound to miR-185-5p to up-regulate KAT7 and thus inhibited cardiomyocyte hypertrophy.

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lncRNA ADAMTS9-AS1/miR-185-5p/KAT7 ceRNA网络抑制肥厚性阻塞性心肌病的心肌细胞肥厚。

肥厚性阻塞性心肌病(HOCM)是一种公认的遗传性心脏病。本研究旨在探讨lncRNA ADAMTS9反义RNA 1 (ADAMTS9- as1)在hocm诱导心肌细胞肥厚中的作用。采集HOCM患者血清。用异丙肾上腺素(ISO)处理AC16细胞，并用e- adamts9 - as1载体、miR-185-5p模拟物和赖氨酸乙酰转移酶7 (KAT7)特异性小干扰RNA转染。采用qRT-PCR或Western blot检测血清或细胞中的lncRNA ADAMTS9-AS1、miR-185-5p、KAT7、脑钠肽(BNP)、房钠肽(ANP)。采用Texas Red-Phalloidin染色法观察细胞表面积。采用核/细胞质分离法检测lncRNA ADAMTS9-AS1的亚细胞定位，采用RNA下拉和双荧光素酶法验证基因相互作用。在HOCM患者和iso处理的AC16细胞的血清中，lncRNA ADAMTS9-AS1下调。lncRNA ADAMTS9-AS1过表达抑制iso诱导的心肌细胞肥大，降低ANP和BNP水平。lncRNA ADAMTS9- AS1位于细胞质中，通过靶向结合抑制miR-185-5p的表达。miR-185-5p结合KAT7 3'UTR并抑制KAT7的表达。miR-185-5p过表达和KAT7敲低均可中和lncRNA ADAMTS9-AS1在心肌细胞肥厚中的抑制作用。总体而言，lncRNA ADAMTS9-AS竞争性地结合miR-185-5p上调KAT7，从而抑制心肌细胞肥大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomedical Research-tokyo 医学-医学：研究与实验

CiteScore

2.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..