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Downregulation of long noncoding RNA SNHG6 rescued propofol-induced cytotoxicity in human induced pluripotent stem cell-derived cardiomyocytes.

ABSTRACT: Background:Propofol (PPF) overdose is a rare but lethal condition, which may lead to severe cardiac failure. In this study, we established an in vitro PPF-induced cardiac cytotoxicity model, and investigate the functional role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6). Methods:Human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) were exposed to PPF in vitro. PPF-induced cytotoxic effects were measured. PPF-induced SNHG6 expression change in HiPSC-CMs were monitored by qRT-PCR. SNHG6 was downregulated in HiPSC-CMs to examine its role in PPF-induced cardiac cytotoxicity. The expression of competing endogenous RNA (ceRNA) candidate of SNHG6, human microRNA-186-5p (hsa-miR-186-5p) was also investigated in PPF-exposed HiPSC-CMs. Functions of hsa-miR-186-5p were further investigated in PPF-exposed and SNHG6-downregulated HiPSC-CMs. Results:PPF induced significant cytotoxicity, as well as SNHG6 upregulation in HiPSC-CMs. SNHG6 downregulation had rescuing effects on PPF-induced cardiac cytotoxicity. Dual-luciferase activity assay confirmed that hsa-miR-186-5p was the ceRNA candidate of SNHG6. QRT-PCR showed hsa-miR-186-5p expression was reversely correlated with SNHG6 in PPF-exposed HiPSC-CMs. Suppressing hsa-miR-186-5p reduced the rescuing effects of SNHG6-downregulation on PPF-induced cardiac cytotoxicity. Conclusions:SNHG6/hsa-miR-186-5p can modulate PPF-induced cardiac cytotoxicity in HiPSC-CMs, and thus may be a future drug target to prevent PPF infusion syndrome.

SUBMITTER: Ren Z

PROVIDER: S-EPMC7487409 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Downregulation of long noncoding RNA SNHG6 rescued propofol-induced cytotoxicity in human induced pluripotent stem cell-derived cardiomyocytes.

Ren Zhongguo Z Hu Rong R

Cardiovascular diagnosis and therapy 20200801 4

<h4>Background</h4>Propofol (PPF) overdose is a rare but lethal condition, which may lead to severe cardiac failure. In this study, we established an <i>in vitro</i> PPF-induced cardiac cytotoxicity model, and investigate the functional role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6).<h4>Methods</h4>Human induced pluripotent stem cell-derived cardiomyocytes (HiPSC-CMs) were exposed to PPF <i>in vitro</i>. PPF-induced cytotoxic effects were measured. PPF-induced SNHG6 ...[more]

PMID: 32968636

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Downregulation of long noncoding RNA SNHG6 rescued propofol-induced cytotoxicity in human induced pluripotent stem cell-derived cardiomyocytes.

Publications

Downregulation of long noncoding RNA SNHG6 rescued propofol-induced cytotoxicity in human induced pluripotent stem cell-derived cardiomyocytes.

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