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Long non‐coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia‐reperfusion injury
Author(s) -
Zhao Zhihui,
Hao Wei,
Meng Qingtao,
Du Xiaobing,
Lei Shaoqing,
Xia Zhongyuan
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10701
Subject(s) - malat1 , downregulation and upregulation , gene knockdown , apoptosis , lactate dehydrogenase , reperfusion injury , pharmacology , ischemia , hypoxia (environmental) , medicine , chemistry , long non coding rna , gene , biochemistry , enzyme , organic chemistry , oxygen
Long non‐coding (lncRNA) MALAT1 can be increased by hypoxia or ischemic limbs. Also, downregulation of MALAT1 contributes to reduction of cardiomyocyte apoptosis. However, the functional involvement of MALAT1 in myocardial ischemia‐reperfusion (I/R) injury has not been defined. This study investigated the functional involvement of lncRNA‐MALAT1 in cardioprotective effects of fentanyl. HL‐1, a cardiac muscle cell line from the AT‐1 mouse atrial cardiomyocyte tumor lineage was pre‐treated with fentanyl and generated cell model of hypoxia‐reoxygenation (H/R). Relative expression of MALAT1, miR‐145, and Bnip3 mRNA in cells was determined by quantitative real‐time PCR. Cardiomyocyte H/R injury was indicated by lactate dehydrogenase (LDH) release and cell apoptosis. The results showed that fentanyl abrogates expression of responsive gene for H/R and induces downregulation of MALAT1 and Bnip3 and upregulation of miR‐145. We found that miR‐145/Bnip3 pathway was negatively regulated by MALAT1 in H/R‐HL‐1 cell with or without fentanyl treatment. Moreover, both MALAT1 overexpression and miR‐145 knockdown reverse cardioprotective effects of fentanyl, as indicated by increase in LDH release and cell apoptosis. The reversal effect of MALAT1 for fentanyl is confirmed in cardiac ischemia/reperfusion (I/R) mice. In summary, lncRNA‐MALAT1 is sensitive to H/R injury and abrogates cardioprotective effects of Fentanyl by negatively regulating miR‐145/Bnip3 pathway.