LncRNA-MALAT1 promotes CPC proliferation and migration in hypoxia by up-regulation of JMJD6 via sponging miR-125

The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for M1-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HE A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear. In this work, we discovered that CoCl2-induced hypoxia can promote CPC proliferation and migration. Additionally, long non-coding RNA MALATI expression was significantly up regulated in the CoCl2-induced hypoxia CPC model. MALATI suppression inhibited CPC proliferation and migration under hypoxic conditions. In addition, MALATI acted as a sponge for miR-125. The miR-125 inhibitor restored the proliferation and migration potentials of CPCs after a MALATI knockdown in hypoxia. A further study demonstrated that JMJD6 was a target of miR-125 whose expression was negatively regulated by miR-125. JMJD6 knockdown blocked miR-125 inhibitor's protective effect on CPC function in hypoxia. Ultimately, our finding demonstrated that MALAT1 can modulate CPC proliferation and migration potential through the miR-125/JMJD6 axis in hypoxia. Our finding provided a new regulatory mechanism for CPC proliferation in hypoxia, which provided a new target for MI-induced HF therapy. (C) 2018 Elsevier Inc. All rights reserved.