PMID- 35251768 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220308 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 27 DP - 2022 Mar 8 TI - Overexpression of cytosolic long noncoding RNA cytb protects against pressure-overload-induced heart failure via sponging microRNA-103-3p. PG - 1127-1145 LID - 10.1016/j.omtn.2022.02.002 [doi] AB - Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. To date, only limited studies have reported the role of mitochondria-derived lncRNAs in heart failure (HF). In the current study, recombinant adeno-associated virus 9 was used to manipulate lncRNA cytb (lnccytb) expression in vivo. Fluorescence in situ hybridization (FISH) assay was used to determine the location of lnccytb, while microRNA (miRNA) sequencing and bioinformatics analyses were applied to identify the downstream targets. The competitive endogenous RNA (ceRNA) function of lnccytb was evaluated by biotin-coupled miRNA pull-down assays and luciferase reporter assays. Results showed that lnccytb expression was decreased in the heart of mice with transverse aortic constriction (TAC), as well as in the heart and plasma of patients with HF. FISH assay and absolute RNA quantification via real-time reverse transcription PCR suggested that the reduction of the lnccytb transcripts mainly occurred in the cytosol. Upregulation of cytosolic lnccytb attenuated cardiac dysfunction in TAC mice. Moreover, overexpression of cytosolic lnccytb in cardiomyocytes alleviated isoprenaline-induced reactive oxidative species (ROS) production and hypertrophy. Mechanistically, lnccytb acted as a ceRNA via sponging miR-103-3p, ultimately mitigating the suppression of PTEN by miR-103-3p. In summary, we demonstrated that the overexpression of cytosolic lnccytb could ameliorate HF. CI - (c) 2022 The Author(s). FAU - Zhang, Xudong AU - Zhang X AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Yuan, Shuai AU - Yuan S AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Liu, Jingbo AU - Liu J AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Tang, Yuyan AU - Tang Y AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Wang, Yan AU - Wang Y AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Zhan, Jiabing AU - Zhan J AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Fan, Jiahui AU - Fan J AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Nie, Xiang AU - Nie X AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Zhao, Yanru AU - Zhao Y AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Wen, Zheng AU - Wen Z AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Li, Huaping AU - Li H AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Chen, Chen AU - Chen C AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. FAU - Wang, Dao Wen AU - Wang DW AD - Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, China. LA - eng PT - Journal Article DEP - 20220210 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC8881631 OTO - NOTNLM OT - GRSF1 OT - PTEN OT - ceRNA OT - cytosol OT - heart failure OT - lncRNA OT - miR-103-3p COIS- The authors declare no competing interests. EDAT- 2022/03/08 06:00 MHDA- 2022/03/08 06:01 PMCR- 2022/02/10 CRDT- 2022/03/07 06:06 PHST- 2021/06/13 00:00 [received] PHST- 2022/02/06 00:00 [accepted] PHST- 2022/03/07 06:06 [entrez] PHST- 2022/03/08 06:00 [pubmed] PHST- 2022/03/08 06:01 [medline] PHST- 2022/02/10 00:00 [pmc-release] AID - S2162-2531(22)00030-0 [pii] AID - 10.1016/j.omtn.2022.02.002 [doi] PST - epublish SO - Mol Ther Nucleic Acids. 2022 Feb 10;27:1127-1145. doi: 10.1016/j.omtn.2022.02.002. eCollection 2022 Mar 8.