Title:Long Noncoding RNA OIP5-AS1 Overexpression Promotes Viability and Inhibits High Glucose-Induced Oxidative Stress of Cardiomyocytes by Targeting MicroRNA-34a/SIRT1 Axis in Diabetic Cardiomyopathy
Volume: 21
Issue: 11
Author(s): Haiyun Sun, Chong Wang, Ying Zhou and Xingbo Cheng*
Affiliation:
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, 215006,China
Keywords:
Diabetic cardiomyopathy, long noncoding RNA, OIP5-AS1, microRNA-34a, SIRT1, oxidative stress.
Abstract:
Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes.
This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1)
on the viability and oxidative stress of cardiomyocyte in DCM.
Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by
qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells.
The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen
species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to
evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was
used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied
to analyze the protein expression of SIRT1.
Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated.
The functional experiment stated that OIP5-AS1 overexpression increased the viability and
SOD level while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical
experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the
complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression
of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the
promoting effect on viability and mitigated the reduction effect on oxidative stress caused by
OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells.
Conclusion: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte
via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for
DCM.
