Long non-coding RNA SNHG1 protects human AC16 cardiomyocytes from doxorubicin toxicity by regulating miR-195/Bcl-2 axis.

Sisi Chen,Yanli Zhou,Jichun Wang

doi:10.1042/bsr20191050

Sisi Chen, Yanli Zhou + Show 1 more

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https://doi.org/10.1042/bsr20191050

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Abstract

Doxorubicin (DOX) is a highly effective anti-tumor drug, but its cardiotoxicity largely restricts its clinical application. The present study was designed to explore whether in vitro DOX toxicity in AC16 cardiomyocytes can be regulated by long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) and to elucidate the underlying mechanisms. We found that DOX treatment led to severe damage in AC16 cells through decreasing cell viability and increasing cell apoptosis. DOX treatment also reduced the expression of SNHG1 in AC16 cells, and overexpression of SNHG1 alleviated the increased apoptosis in DOX-treated AC16 cells. Moreover, we found that SNHG1 could counteract the inhibitory effect of miR-195 on Bcl-2, and miR-195 restoration blocked the beneficial effect of SNHG1 against DOX toxicity in AC16 cells. In short, the present study provided convincing evidence that SNHG1 protects human AC16 cardiomyocytes from DOX toxicity partly by regulating miR-195/Bcl-2 axis.

Highlights

Cancer is the main cause of deaths worldwide
To further investigate the role of small nucleolar RNA host gene 1 (SNHG1) in DOX toxicity, SNHG1 was overexpressed in DOX-treated AC16 cells, and the successful transfection was verified by RT-Quantitative PCR (qPCR) analysis (Figure 2A)
DOX cardiotoxicity remains a tough problem for both cardiologists and oncologists, and the underlying mechanisms have been extensively studied since DOX was first used

Summary

Introduction

Cancer is the main cause of deaths worldwide. Doxorubicin (DOX), an anthracycline antibiotic derived from Streptomyces, is one of the most powerful and widely used anti-tumor drugs [1]. The clinical application of this drug is largely limited by the toxic side effects on healthy human organs, heart [2]. 10% of patients treated with DOX or its derivatives will develop cardiac complications [3]. LncRNA small nucleolar RNA host gene 1 (SNHG1), located in human chromosome 11, was found to be aberrantly expressed in a wide variety of human cancers [5]. Zhang et al [6] reported that SNHG1 attenuated the effects of H2O2 on the viability and apoptosis of human cardiomyocytes. In this study, using in vitro DOX-treated AC16 cardiomyocytes, our major purpose was to explore whether DOX toxicity can be regulated by SNHG1 and to elucidate the underlying mechanisms

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