Effect of lncRNA MALAT1 on rats with myocardial infarction through regulating ERK/MAPK signaling pathway
Authors: S Wang
Q-Z Zhang
G-J Tan
H Huang
Y-Z Fan
Journal: European Review for Medical and Pharmacological Sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA MALAT1; myocardial infarction; ERK/MAPK signaling pathway; SD rats; cardiac function
Affiliations: Department of Cardiology, Xiangtan Central Hospital, Xiangtan, China. .

Abstract:  Objective: To explore the effect of the long non-coding ribonucleic acid (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on rats with myocardial infarction (MI) by regulating the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway. Materials and methods: The Sprague- Dawley (SD) rat model of MI was established, and lncRNA MALAT1 was overexpressed using pcDNA-MALAT1 plasmids (MALAT1 group, n=10) and silenced using RNA interference technique (siMALAT1 group, n=10). The Sham group (n=10) was also set up. The transfection efficiency of lncRNA MALAT1 in rats was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). 2 weeks after the successful modeling, the cardiac function indexes were measured through magnetic resonance imaging (MRI) and echocardiography (ECG). The myocardial tissue injury was observed via hematoxylin-eosin (HE) staining, and the apoptosis of myocardial tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the levels of the serum inflammatory factors were detected via enzyme-linked immunosorbent assay (ELISA), the messenger RNA (mRNA) expressions of Collagen I and III, the apoptosis, the and pathway genes were detected via RT-PCR. The expressions of ERK/MAPK pathway-related proteins in myocardial tissues were detected via Western blotting. Results: The expression of lncRNA MALAT1 was remarkably increased in the MALAT1 group but evidently declined in the siMALAT1 group (p&lt;0.05), indicating the successful transfection. The fractional shortening (FS, %) and ejection fraction (EF, %) were significantly restored in siMALAT1 group (p&lt;0.05), suggesting that the silence of MALAT1 can improve the cardiac function after acute MI. The results of the HE staining and TUNEL assay manifested that siMALAT1 group had milder myocardial injury and decreased apoptosis compared with MALAT1 group. In the MALAT1 group, the mRNA expressions of Collagen I and III, Caspase3, ERK2, and MAPK were remarkably increased (p&lt;0.05), while the mRNA expression of Bcl-2 was remarkably decreased (p&lt;0.05). The above expressions had the opposite trends in siMALAT1 group. Besides, the protein expressions of ERK2 and MAPK in MALAT1 group were significantly increased (p&lt;0.05). Conclusions: The downregulation of lncRNA MALAT1 can significantly improve the cardiac function after MI in SD rats mainly by inhibiting the ERK/MAPK pathway. 

Retracted: No

PubPeer comments:
 Figure 2:  HE staining of heart. A, MALAT1 group (u00d710). B, siMALAT1 group (u00d710). The myocardial cells are disorderly arranged and the muscle fibers are thickened in the MALAT1 group. In the siMALAT1 group, the myocardial injury almost cannot be observed .  Please compare the MALAT1 example with the SHR example of Figure 3 from [Shi et al (2019)]  Pathological changes in myocardial tissues of rats in each group detected via HE staining .  , 
  Figure 3. Apoptosis detected via TUNEL staining. There is almost no myocardial apoptosis in the Sham group (u00d740), a large number of apoptotic cells in the MALAT1 group (u00d740), and remarkably decreased myocardial apoptosis in the siMALAT1 group .  , 
 #1 Another sighting of Fig 2! Figure 3A from [Wang et al (2019)] .  HE staining results of rat heart. A, Model group (u00d710). B, Treatment group (u00d710). Disorderly-arranged myocardial cells and thickened muscle fibers are detected in the model group, while almost no myocardial injury is found in the treatment group.  , 
 #1 Fig 2B:  Fig 3C from [Zeng et al (2019)] :  HE staining of rat s heart. A, Sham group, B, AMI group, C, ATV-AMI group .  , 
 Because these papers all have at least one image in common, while not sharing any authors or affiliations, they appear to be produced by a paper mill, which might have supplied the papers and the figures. As of today, this set contains at least 9 papers, all connected to each other with at least one photo, as per the work of Hoya Camphorifolia. * H. Wang et al. - DOI: 10.26355 eurrev_201912_19695 - https: pubpeer.com publications 7BB185FB656F0F8214F92EDFE047FF * HT Zeng et al. - DOI: 10.26355 eurrev_201908_18757 - https: pubpeer.com publications B226E56465DACEA93791215756340B * MH Lun et al. - DOI: 10.26355 eurrev_202005_21366 - https: pubpeer.com publications AAA8F559D37A6D853CC16764A06A53 * Q Xu et al. - DOI: 10.26355 eurrev_201909_19026 - https: pubpeer.com publications C6F5DA3CA8F64BD57CE8A9B38616D0 * YJ Shi et al. - DOI: 10.26355 eurrev_201906_18082 - https: pubpeer.com publications 153695342827B732C15C614F61DF10 * YJ Wan et al. - DOI: 10.26355 eurrev_201908_18622 - https: pubpeer.com publications 41C0C61998A1A6C6339689A61A6ABF * YT Zhu et al. - DOI: 10.26355 eurrev_202005_21205 - https: pubpeer.com publications 277C24C645B71AF55A72A1200C46B4 * YY Wang et al. - DOI: 10.26355 eurrev_201912_19696 - https: pubpeer.com publications 702E90DEA6ED9278B2F67828C5329D * YZ Fan et al. - DOI: 10.26355 eurrev_201910_19306 - https: pubpeer.com publications 0B80BCE778E3D360504102D662CDE5 , 
 Primers for rat Caspase, as in Article:  Primer-Blast for rat:  Primers for rat u03b2-actin, as in Article:  Primer-Blast for rat:  587bp is far too long of an amplicon size to be detected by qPCR. Primer for rat Bcl-2, as in Article:  Primer-Blast for rat:  Primers for rat U6, as in Article: seems OK  Primer-Blast for rat (nr template): sole match  ,