Overexpression of microRNA‐590‐3p promotes the proliferation of and inhibits the apoptosis of myocardial cells through inhibition of the NF‐κB signaling pathway by binding to RIPK1
Authors: Jing Jiang
Can Zhao
Yong-Quan Wu
Yong-Liang Wang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: microRNA-590-3p; myocardial ischemia/reperfusion injury; nuclear factor kappa-B (NF-κB); oxidative stress (OS); receptor-interacting protein kinase 1 (RIPK1).
Affiliations: Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Department of Cardiology, Chinese People's Liberation Army 401st Hospital, Qingdao, China., Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Abstract:  Ischemic heart disease is widely considered as a major health threat, which causes a high number of deaths every year worldwide. Much evidence has shown that oxidative stress (OS) is implicated in the pathogenesis of ischemia-reperfusion injury (IRI). This study aims to evaluate the effect of miR-590-3p on the OS of IRI mice through the nuclear factor kappa-B (NF-κB) signaling pathway by targeting receptor-interacting protein kinase 1 (RIPK1). IRI mouse models were established for extracting myocardial tissues and isolating myocardial cells. The expression of inflammatory related-factors was detected by enzyme-linked immunosorbent assay, and superoxide dismutase (SOD) and malondialdehyde (MDA) in tissues were determined. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were performed to assess the role of miR-590-3p in the expression of NF-κB-related factors and apoptosis-related factors. Besides, the regulatory effects of miR-590-3p on myocardial cell proliferation and apoptosis were also assessed. According to the obtained results, we found that IRI mice displayed higher expression of tumor necrosis factor-α, interleukin (IL)-6, and interferon-γ, lower expression of IL-10 in serum, a decreased SOD level, and an increased MDA level. In addition, RIPK1 was determined as a target gene of miR-590-3p. After transfection of overexpressed miR-590-3p or si-RIPK1, declined RIPK1, NF-κB, Toll-like receptor 4, caspase-3, FasL, p53, and c-myc levels, increased B-cell lymphoma-2 level, promoted cell proliferation, promoted cell cycle distribution and inhibited apoptosis of myocardial cells were found. Our study demonstrates that miR-590-3p can alleviate the OS of IRI mice through the inhibition of the RIPK1 and NF-κB signaling pathway. Thus, miR-590-3p represents a potential target for IRI repair. 

Retracted: Yes

PubPeer comments:
 Fig 9A.  proportion of cell cycle in different groups by PI single staining . Overhangs? Were these flow-cytometry plots hand-drawn? ![file] , 
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 15 October 2018 in Wiley Online Library , has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially but were not available for a final confirmation of the retraction note. , 
 Here are four line-ups of excised rodent hearts, subsequent to infarcts and myocardial ischaemic-reperfusion injuries. Clockwise from upper left: Fig 4a from [Wu, Wu Ni (2019)] ,  photographs of [myocardial infarct size] in **rats** treated with miR-202-3p mimic, siRNATRPM6, miR-202-3p inhibitor or miR-202-3p inhibitor + siRNA-TRPM6 after 4 weeks (the white area was the infarction area) . Fig 2A from [Ge et al (2019)] :  myocardial tissues stained by TTC of **mice** treated with miR-26b agomir, miR-26b antagomir and or NS-398 (seven days after infarction). Fig 1A from **[Zhao et al (2019)] **.  TTC staining results revealed obvious IS in IRI **mice** (two weeks after infarction). Fig 5A from [Li et al (2019)] ,  Representative images of myocardial infarct in shamu2010operated and MI **rats** detected by triphenyltetrazolium chloride staining (seven days after infarction). ![] The same rough-textured surface appears throughout these images from different laboratories, allowing us to rescale them to a common scale: ![file] Two mouse hearts and two rat hearts are similar sizes. Is this correct? ,