Department of Cardiovascular, The First Affiliated Hospital of USTC, Hefei 230001, Anhui, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China.
Department of Cardiovascular, The First Affiliated Hospital of USTC, Hefei 230001, Anhui, China; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China.
Biomed Pharmacother. 2018 Oct;106:738-746. doi: 10.1016/j.biopha.2018.06.122. Epub 2018 Jul 11.
Long noncoding RNA (LncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development of acute myocardial infarction (AMI). However, the molecular mechanism and biological function of MALAT1 in AMI remained unclear.
The expression levels of MALAT1, miR-320 and phosphatase and tensin homolog deleted on chromosome 10 (Pten) in a mouse model of AMI and sham-operated mice were determined by quantitative real-time PCR (qRT-PCR) and western blotting, respectively. The relationships between miR-320 and MALAT1, Pten were confirmed by luciferase reporter assay. The roles of MALAT1, miR-320 and Pten in myocardial apoptosis were evaluated using Annexin V-FITC/PI double-labeled flow cytometry. Echocardiographic evaluation, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarct size and myocardial apoptosis using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were used to examine the impact of MALAT1 on myocardial injury.
MALAT1 and Pten were highly expressed, while miR-320 was suppressed in MI group. Mechanistically, MALAT1 may serve as a sponge for miR-320 to upregulate Pten, a direct target of miR-320. Moreover, MALAT1 knockdown overturned the pro-apoptotic effect of miR-320 in vitro and in vivo.
MALAT1 knockdown attenuated myocardial apoptosis through suppressing Pten expression by sponging miR-320 in mouse AMI.
长链非编码 RNA（LncRNA）转移相关肺腺癌转录本 1（MALAT1）参与急性心肌梗死（AMI）的发生。然而，MALAT1 在 AMI 中的分子机制和生物学功能仍不清楚。
通过定量实时 PCR（qRT-PCR）和 Western blot 分别检测 AMI 模型小鼠和假手术小鼠中 MALAT1、miR-320 和 10 号染色体缺失的磷酸酶和张力蛋白同源物（Pten）的表达水平。通过荧光素酶报告基因检测证实 miR-320 与 MALAT1、Pten 的关系。采用 Annexin V-FITC/PI 双标记流式细胞术评估 MALAT1、miR-320 和 Pten 在心肌细胞凋亡中的作用。通过超声心动图评估、血清肌酸激酶同工酶 MB（CK-MB）和乳酸脱氢酶（LDH）、心肌梗死面积和末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）检测评估 MALAT1 对心肌损伤的影响。
MALAT1 和 Pten 表达升高，miR-320 表达受抑在 MI 组。在机制上，MALAT1 可能作为 miR-320 的海绵体，上调 miR-320 的直接靶标 Pten。此外，MALAT1 敲低在体外和体内逆转了 miR-320 的促凋亡作用。
MALAT1 敲低通过海绵吸附 miR-320 抑制 Pten 表达，减轻小鼠 AMI 中的心肌细胞凋亡。
