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Activation of cell apoptosis is a major form of cell death during myocardial ischemia\/reperfusion injury (I\/RI). Therefore, examining ways to control cell apoptosis has important clinical significance for improving postischemic recovery. Clinical evidence demonstrated that miR-181c-5p was significantly upregulated in the early phase of myocardial infarction. However, whether or not miR-181c-5p mediates cardiac I\/RI through cell apoptosis pathway is unknown. Thus, the present study is aimed at investigating the role and the possible mechanism of miR-181c-5p in apoptosis during I\/R injury by using H9C2 cardiomyocytes. <jats:italic>Methods and Results<\/jats:italic>. The rat origin H9C2 cardiomyocytes were subjected to hypoxia\/reoxygenation (H\/R, 6 hours hypoxia followed by 6 hours reoxygenation) to induce cell injury. The results showed that H\/R significantly increased the expression of miR-181c-5p but not miR-181c-3p in H9C2 cells. In line with this, in an <jats:italic>in vivo<\/jats:italic> rat cardiac I\/RI model, miR-181c-5p expression was also significantly increased. The overexpression of miR-181c-5p by its agomir transfection significantly aggravated H\/R-induced cell injury (increased lactate dehydrogenase level and reduced cell viability) and exacerbated H\/R-induced cell apoptosis (greater cleaved caspases 3 expression, Bax\/Bcl-2 and more TUNEL-positive cells). In contrast, inhibition of miR-181c-5p <jats:italic>in vitro<\/jats:italic> had the opposite effect. By using computational prediction algorithms, protein tyrosine phosphatase nonreceptor type 4 (PTPN4) was predicted as a potential target gene of miR-181c-5p and was verified by the luciferase reporter assay. The overexpression of miR-181c-5p significantly attenuated the mRNA and protein expression of PTPN4 in H9C2 cardiomyocytes. Moreover, knockdown of PTPN4 significantly aggravated H\/R-induced enhancement of LDH level, cleaved caspase 3 expression, and apoptotic cell death, which mimicked the proapoptotic effects of miR-181c-5p in H9C2 cardiomyocytes. <jats:italic>Conclusions<\/jats:italic>. These findings suggested that miR-181c-5p exacerbates H\/R-induced cardiomyocyte injury and apoptosis <jats:italic>via<\/jats:italic> targeting PTPN4 and that miR-181c-5p\/PTPN4 signaling may yield novel strategies to combat myocardial I\/R injury.<\/jats:p>","DOI":"10.1155\/2019\/1957920","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T19:43:22Z","timestamp":1555530202000},"page":"1-15","source":"Crossref","is-referenced-by-count":46,"title":["miR-181c-5p Exacerbates Hypoxia\/Reoxygenation-Induced Cardiomyocyte Apoptosis via Targeting PTPN4"],"prefix":"10.1155","volume":"2019","author":[{"given":"Liang","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The First Hospital, Jilin University, Jilin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong 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