PMID- 34968461 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20220531 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 916 DP - 2022 Feb 5 TI - Long non-coding RNA MALAT1 modulates myocardial ischemia-reperfusion injury through the PI3K/Akt/eNOS pathway by sponging miRNA-133a-3p to target IGF1R expression. PG - 174719 LID - S0014-2999(21)00875-X [pii] LID - 10.1016/j.ejphar.2021.174719 [doi] AB - The mechanism of myocardial ischemia-reperfusion injury (MIRI) is a complex pathophysiological process that can lead to poor patient outcomes. Although LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia reperfusion (IR) injury, the specific mechanism remains largely unknown. This study aimed to elucidate the roles and possible mechanism of MALAT1 in myocardial IR injury. IR model was established in rats by ligation of the anterior descending artery in vivo, and H9c2 and HL-1 cells were treated by hypoxia/reoxygenation (HR) to construct the model in vitro. The small interfering RNA (siRNA) for MALAT1 and miR-133a-3p mimics, inhibitor was used to transfect the cells. The expression of MALAT1, miR-133a-3p in MIRI were evaluated using real-time quantitative polymerase chain reaction (qRT-PCR)，immunohistochemistry (IHC) and western blot (WB). Relationships between MALAT1, insulin-like growth factor 1 receptor (IGF1R) with miR-133a-3p were confirmed by luciferase reporter assay. Annexin V-FITC/PI double-labeled flow cytometry, terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Cell Counting Kit-8 (CCK-8), serum creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were evaluated to examine the impact of MALAT1 on MIRI. Our results revealed that MALAT1 was highly expressed, while miR-133a-3p and IGF1R were repressed in IR and HR groups. Knockdown of MALAT1 alleviate the pro-apoptotic effect and myocardial injury in vitro and in vivo. Systematically, MALAT1 may serve as a sponge for miR-133a-3p to suppress IGF1R, which a direct target of miR-133a-3p, then inhibit the PI3K/Akt/eNOS survival pathway. Mechanistically, our study demonstrated that MALAT1 regulates PI3K/Akt/eNOS signaling via miR-133a-3p. In summary, these results suggest that MALAT1 and miR-133a-3p play important roles in MIRI. MALAT1 regulates miR-133a-3p /IGF1R axis. These results show light on the underlying mechanisms of MIRI and provide potential therapeutic targets for MIRI. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Liu, Xin-Ming AU - Liu XM AD - Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. FAU - Zhang, Zhenzhou AU - Zhang Z AD - Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. FAU - Zhong, Jiuchang AU - Zhong J AD - Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. FAU - Li, Ning AU - Li N AD - National Institute of Biological Sciences, Beijing, China. FAU - Wang, Tao AU - Wang T AD - National Institute of Biological Sciences, Beijing, China. FAU - Wang, Lefeng AU - Wang L AD - Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. FAU - Zhang, Qian AU - Zhang Q AD - Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. Electronic address: zqian604@163.com. LA - eng PT - Journal Article DEP - 20211227 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Igf1r protein, rat) RN - 0 (MALAT1 long noncoding RNA, rat) RN - 0 (MIRN133 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 2.7.10.1 (Receptor, IGF Type 1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Apoptosis/genetics MH - *MicroRNAs/genetics/metabolism MH - *Myocardial Reperfusion Injury/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - *RNA, Long Noncoding/genetics/metabolism MH - Rats MH - Receptor, IGF Type 1 OTO - NOTNLM OT - Apoptosis OT - IFG1R OT - Ischemia reperfusion (IR) OT - MALAT1 OT - miR-133a-3p EDAT- 2021/12/31 06:00 MHDA- 2022/04/08 06:00 CRDT- 2021/12/30 20:12 PHST- 2021/07/10 00:00 [received] PHST- 2021/12/07 00:00 [revised] PHST- 2021/12/20 00:00 [accepted] PHST- 2021/12/31 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2021/12/30 20:12 [entrez] AID - S0014-2999(21)00875-X [pii] AID - 10.1016/j.ejphar.2021.174719 [doi] PST - ppublish SO - Eur J Pharmacol. 2022 Feb 5;916:174719. doi: 10.1016/j.ejphar.2021.174719. Epub 2021 Dec 27.