LncRNA MIAT knockdown alleviates oxygen-glucose deprivation‑induced cardiomyocyte injury by regulating JAK2/STAT3 pathway via miR-181a-5p

Published:September 03, 2021DOI:https://doi.org/10.1016/j.jjcc.2021.08.018


      • 1
        Myocardial infarction-associated transcript (MIAT) was upregulated in oxygen-glucose deprivation (OGD)-induced cardiomyocytes.
      • 2
        MIAT silencing alleviated the injury of cardiomyocytes induced by OGD.
      • 3
        MIAT sponged miR-181a-5p to regulate the JAK2/STAT3 axis.
      • 4
        JAK2 overexpression or miR-181a-5p inhibition reversed the regulatory effects of MIAT silencing in OGD-induced cardiomyocyte damage.



      Coronary artery disease (CAD) is a common heart disease with high incidence and mortality. Myocardial ischemia is the main type of CAD, which negatively affects health worldwide. The aim of the present study was to investigate the function and mechanism of myocardial infarction-associated transcript (MIAT) in myocardial ischemia.


      Human cardiomyocytes (HCM) were treated with oxygen-glucose deprivation (OGD) to set the in vitro model and mouse myocardial ischemia/reperfusion (I/R) was set for in vivo model. Cell viability and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and immunofluorescence analysis. Inflammatory cytokines levels were detected by enzyme-linked immunosorbent assay. Gene and protein expressions were identified by quantitative real time-polymerase chain reaction or Western blotting. The interaction of MIAT, miR-181a-5p, and janus kinase 2 (JAK2) was identified by dual-luciferase report assay. Mouse heart tissues histopathological condition were observed by hematoxylin and eosin assays.


      Expression of MIAT and JAK2 were increased in OGD-treated HCM and mice of I/R model group, and miR-181a-5p was decreased. MIAT silencing could reverse the OGD treatment induced cell proliferation inhibition, cleaved caspase-3 and Bcl2-associated X (Bax) levels increased, while those of B-cell lymphoma-2 (Bcl-2) and mitochondria's cyt-C decreased. Besides, MIAT knockdown attenuated the OGD-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels. Moreover, MIAT targeted miR-181a-5p to enhance the expression of JAK2 and signal Transducer and Activator of Transcription 3 (STAT3), and miR-181a-5p overexpression promoted proliferation, whereas it inhibited apoptosis in OGD-induced cardiomyocytes. Furthermore, the regulatory effects of MIAT knockdown in cell proliferation, apoptosis, and inflammatory injury was reversed by inhibition of miR-181a-5p or overexpression of JAK2 in OGD-treated HCM. Knockdown of MIAT reduced myocardial injury caused by I/R treatment in vivo.


      MIAT knockdown inhibited apoptosis and inflammation by regulating JAK2/STAT3 signaling pathway via targeting miR-181a-5p in myocardial ischemia model. MIAT can be a possible therapeutic target for controlling the progression of myocardial ischemia.

      Graphical abstract


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