Zhao Pengnan,Luo Guiping,Jiang Yunhan,Li Jingwei,Tang Fuqin,Gu Qiang,Xiao Yingbin.Significance of miR-17-5p in adaptation of chronic hypoxia in myocardium via modulation of STAT3 signaling pathway[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(06):589-594.
Zhao Pengnan,Luo Guiping,Jiang Yunhan,Li Jingwei,Tang Fuqin,Gu Qiang,Xiao Yingbin.Significance of miR-17-5p in adaptation of chronic hypoxia in myocardium via modulation of STAT3 signaling pathway[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(06):589-594.DOI:
Significance of miR-17-5p in adaptation of chronic hypoxia in myocardium via modulation of STAT3 signaling pathway
Objective To explore the expression of miR-17-5p and its effect on STAT3 signaling pathway in the myocardium under chronic hypoxic condition. Methods Twenty children with congenital heart disease
who were prepared to undergo surgical treatment from August 2014 to April 2015
were recruited and divided into 10 cases of cyanotic type (average age 61.5±46.5 months
post-operation diagnosis as Tetralogy of Fallot) and 10 cases of acyanotic type (average age 43.2±32.1 months
post-operation diagnosis as interventricular septal defect and right ventricular outflow tract stenosis). The right myocardial tissue of ventricular outflow tract was taken as the specimen to detect the expression of miR-17-5p by RT-PCR. Chronic hypoxia models of H9c2 cardiomyocytes were established and divided into 5 groups including hypoxia 0-h group
hypoxia 12-h group
hypoxia 24-h group
hypoxia 48-h group and hypoxia 72-h group (n=5)
and RT-PCR was employed to detect the expression of miR-17-5p in each group. H9c2 cardiomyocytes were transfected with antagomir miR-17-5p and agomir miR-17-5p by liposomes to build miR-17-5p overexpression and silence models of H9c2 cardiomyocytes
and then the cells were cultured in hypoxia incubator for 48 h. CCK8 assay was used to detect cell proliferation
TUNEL method was adopted to detect cell apoptosis
and Western blotting was employed to detect the expressions of STAT3
p-Tyr-705-STAT3 and downstream c-myc. Results Compared with the acyanosis group (0.482±0.163)
the miR-17-5p expression of the cyanotic group (1.45±0.705) was significantly higher (P0.01). The chronic hypoxia cell model showed that the expression of miR-17-5p was increased gradually along with chronic hypoxia time (P0.01). Overexpression of miR-17-5p inhibited cardiomyocyte proliferation and promoted apoptosis significantly through inhibiting the expression of STAT3
p-Tyr-705-STAT3 and c-myc (P0.01). The inhibition of miR-17-5p had no effect on the expression of p-Tyr-705-STAT3
STAT3 and c-myc
and the changes of proliferation and apoptosis of cardiomyocytes (P0.05). Conclusion During chronic hypoxia
miR-17-5p may be involved in the regulation of STAT3-c-myc signal pathway
and has important significance in survival and function regulation of cardiomyocytes.