未经批准:蒽环类药物(ANT)是必不可少的化学治疗剂;然而,它们的副作用可能导致癌症幸存者的心力衰竭。虽然长非编码RNA(lncRNAs)已经成为细胞过程中的新参与者,对蒽环类药物诱导的心脏毒性相关的lncRNA表达的了解有限。这项研究调查了暴露于3种流行的ANT的人类心脏微组织中的lncRNA谱,即阿霉素,表柔比星,和伊达比星,以及在接受ANT治疗的患者的心脏活检中。
UNASSIGNED:在2周内将体外微组织以2剂量暴露于每种ANT;在7个时间点收集转录组数据。从接受ANT治疗的心力衰竭患者和对照受试者收集人活检。与对照样品相比,超过100个lncRNA在每种体外ANT处理条件下差异表达;它们中的16个在所有ANT处理条件下差异表达。lncRNA数据库和文献揭示了这些lncRNA如何与心力衰竭和细胞功能相关的见解。例如,H19和RMRP参与心力衰竭进展,而BDNF-AS是心肌细胞损伤相关基因;SNHG7是心脏肥大调节因子。PCAT19可以促进miR-182/PDK4轴的表达和调节p53的表达,而SNHG29可以通过miR-223-3p/CTNND1轴调节Wnt/β-catenin信号通路。其他lncRNAs,仅在特定的ANT治疗条件下差异表达,也参与心肌细胞损伤和心力衰竭疾病。体外心脏组织中这些lncRNA表达的改变也通过人类活检的类似变化得到证实。
UASSIGNED:这项研究揭示了几种lncRNAs,它们可能是进一步的ANT诱导的心脏毒性研究的潜在生物标志物或靶标,根据转录组,在暴露于ANT的人类心脏微组织以及接受ANT治疗的患者的心脏活检中。尤其是,H19lncRNA显示其对靶毒性的贡献,其中涉及化学抗性和心脏毒性机制。
UNASSIGNED: Anthracyclines (ANTs) are essential chemotherapeutic agents; however, their adverse effects can lead to heart failure in cancer survivors. While long non-coding RNAs (lncRNAs) have become new players in cellular processes, there is limited knowledge on lncRNA expression related to anthracyclines-induced cardiotoxicity. This study investigates the lncRNA profiles in human cardiac microtissues exposed to 3 popular ANTs, namely doxorubicin, epirubicin, and idarubicin, as well as in heart biopsies from ANT-treated patients.
UNASSIGNED: The in vitro microtissues were exposed to each ANT at 2 doses over 2 weeks; the transcriptome data was collected at 7 time points. The human biopsies were collected from heart failure patients who underwent ANT treatment and control subjects. Over 100 lncRNAs were differentially expressed in each in vitro ANT treatment condition compared to control samples; 16 of them were differentially expressed across all ANT-treated conditions. The lncRNA databases and literature revealed insight on how these lncRNAs relate to heart failure and cellular functions. For instance, H19 and RMRP are involved in heart failure progression, while BDNF-AS is a cardiomyocyte damage-associated gene; SNHG7 is a cardiac hypertrophy regulator. PCAT19 can promote the miR-182/PDK4 axis and modulate p53 expression, whereas SNHG29 can regulate the Wnt/β-catenin signaling pathway via the miR-223-3p/CTNND1 axis. Other lncRNAs, which were only differentially expressed in particular ANT-treated conditions, are also involved in cardiomyocyte damage and heart failure disease. The alterations of these lncRNA expressions in the in vitro cardiac tissue were also affirmed by similar changes in the human biopsies.
UNASSIGNED: This study revealed several lncRNAs that can be potential biomarkers or targets for further ANT-induced cardiotoxicity investigation, according to the transcriptome in both human cardiac microtissues expose to ANTs as well as in heart biopies form ANT-treated patients. Especially, H19 lncRNA showed its contribution to on-target toxicity, in which it is involved in both chemoresistance and cardiotoxic mechanism.