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Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with I\/R injury as cardiomyocytes are abundant in mitochondria. SOCS6 is known to participate in mitochondrial fragmentation, but its exact involvement and the pathways associated are uncertain. <jats:italic>Methods and Results<\/jats:italic>. The expression of SOCS6 was analyzed by western blot in cardiomyocytes under a hypoxia and reoxygenation (H\/R) model. A dual\u2010luciferase reporter assay was used to confirm the direct interaction between miR\u201019b and the 3\u2009<jats:sup>\u2032<\/jats:sup>\u2010UTR of Socs6. In the present study, we found that Socs6 inhibition by RNA interference attenuated H\/R\u2010induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that Socs6 is a direct target of miR\u201019b. The overexpression of miR\u201019b decreased mitochondrial fission and apoptosis <jats:italic>in vitro<\/jats:italic>. Moreover, the presence of miR\u201019b reduced the level of SOCS6 and the injury caused by I\/R <jats:italic>in vivo<\/jats:italic>. There were less apoptotic cells in the myocardium of mice injected with miR\u201019b. In addition, we found that the RNA\u2010binding protein, Quaking (QK), participates in the regulation of miR\u201019b expression. <jats:italic>Conclusions<\/jats:italic>. Our results indicate that the inhibition of mitochondrial fission through downregulating Socs6 via the QK\/miR\u201019b\/Socs6 pathway attenuated the damage sustained by I\/R. The QK\/miR\u201019b\/Socs6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.<\/jats:p>","DOI":"10.1155\/2022\/1121323","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T23:35:06Z","timestamp":1643326506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking\u2010Mediated 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