title: Long non-coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia-reperfusion injury.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Zhang Road, Wu chang District No. 99 Jie fang Road 238, 430060, Wuhan, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Inner Mongolia Autonomous Region People's Hospital, Zhao Wu Da Road, No.20, Sai Han District, 010017, Huhhot, Inner Mongolia Autonomous Region, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Zhang Road, Wu chang District No. 99 Jie fang Road 238, 430060, Wuhan, China.
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, Inner Mongolia Autonomous Region People's Hospital, Zhao Wu Da Road, No.20, Sai Han District, 010017, Huhhot, Inner Mongolia Autonomous Region, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Du
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Zhang Road, Wu chang District No. 99 Jie fang Road 238, 430060, Wuhan, China.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Hubei Zhang Road, Wu chang District No. 99 Jie fang Road 238, 430060, Wuhan, China.
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Xia
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002460:Cell Line; D005283:Fentanyl / Q000627:therapeutic use*; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: C508686:BNip3 protein, mouse; D002316:Cardiotonic Agents; C543499:MIRN145a microRNA, mouse; C557040:Malat1 long non-coding RNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D062085:RNA, Long Noncoding; D005283:Fentanyl
keywords: Bnip3; MALAT1; fentanyl; ischemia reperfusion; miR-145