Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner

Zhuang, Aowen; Calkin, Anna C.; Lau, Shannen; Kiriazis, Helen; Donner, D.; Liu, Yingying; Bond, Simon T.; Moody, Sarah; Gould, Eleanor A.M.; Colgan, Timothy D.; Ruiz-Carmona, Sergio; Inouye, Michael; Vallim, Thomas Q. de Aguiar; Tarling, Elizabeth J.; Quaife-Ryan, Gregory A.; Hudson, James E.; Porrello, Enzo R.; Gregorevic, Paul; Gao, Xiao‐Ming; Du, Xiao‐Jun; McMullen, Julie R.; Drew, Brian G.

doi:10.1016/j.isci.2021.102537

Cited by 16 publications

(14 citation statements)

References 56 publications

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“…We have previously described a global Oip5os1 null mouse generated by our laboratory, which demonstrated no detectable expression of Oip5os1 in all tissues analyzed (Zhuang, Calkin, et al., 2021). In brief, the entire genomic location (~13 kb) of this gene was removed in the KO mice, covering everything from the transcriptional start site, all exons and introns, and ending at the final codon of the last exon.…”

Section: Resultsmentioning

confidence: 99%

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Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes

Zhuang,

Tan,

Liu

et al. 2023

Physiological Reports

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Long ncRNAs (lncRNAs) have been shown to play a biological and physiological role in various tissues including the heart. We and others have previously established that the lncRNA Oip5os1 (1700020I14Rik, OIP5‐AS1, Cyrano) is enriched in striated muscles, and its deletion in mice leads to defects in both skeletal and cardiac muscle function. In the present study, we investigated the impact of global Oip5os1 deletion on cardiac function in the setting of streptozotocin (STZ)‐induced diabetes. Specifically, we studied male WT and KO mice with or without diabetes for 24 weeks, and phenotyped animals for metabolic and cardiac endpoints. Independent of genotype, diabetes was associated with left ventricular diastolic dysfunction based on a fall in E'/A' ratio. Deletion of Oip5os1 in a setting of diabetes had no significant impact on ventricular function or ventricular weight, but was associated with left atrial dysfunction (reduced fractional shortening) and myopathy which was associated with anesthesia intolerance and premature death in the majority of KO mice tested during cardiac functional assessment. This atrial phenotype was not observed in WT diabetic mice. The most striking molecular difference was a reduction in the metabolic regulator ERRalpha in the atria of KO mice compared with WT mice. There was also a trend for a reduction in Serca2a. These findings highlight Oip5os1 as a gene of interest in aspects of atrial function in the setting of diabetes, highlighting an additional functional role for this lncRNA in cardiac pathological settings.

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Section: Resultsmentioning

confidence: 99%

“…Oip5os1 knockout (KO) mice were generated in our laboratory on a C57BL/6J background with the Australian Phenomics Network as previously described (Zhuang, Calkin, et al., 2021). Mice were bred as heterozygous parental lines and cohorts of littermate wildtype (WT), and KO mice were generated for subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes

Zhuang,

Tan,

Liu

et al. 2023

Physiological Reports

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“…Among the differentially expressed lncRNAs identified ( Tables 1 , 2 ), Oip5os1 (OIP5-AS1, transcript ID: ENSMUST00000147425, FC = 115.55), UBXN7 (transcript ID: chr16: 32388756-32392334, FC = 101.58), and Snhg12 (transcript ID: ENSMUST00000128131, FC = 44.14) exhibited significantly increased expression levels, while Junos (transcript ID: XR_003955073.1, FC = 0.016) and another transcript of Snhg12 (transcript ID: ENSMUST00000126380, FC = 0.017) exhibited downregulated expression in FDM retinal tissue samples. The lncRNA OIP5-AS1 is involved in the pathogenesis of a variety of diseases, including colon cancer ( Wang Y. et al, 2021 ), prostate cancer ( Zhang Y. et al, 2021 ), papillary thyroid cancer ( Zhang X. et al, 2021 ), and osteosarcoma ( Li et al, 2021 ), as well as heart failure ( Zhuang et al, 2021 ). More importantly, previous evidence has suggested that OIP5-AS1 might participate in the mechanisms of primary open angle glaucoma (POAG) and cataracts ( Zhou et al, 2020 ) ( Jing et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing analysis reveals the long noncoding RNA profile in the mouse myopic retina

et al. 2022

Front. Genet.

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Aim: Myopia is a prevalent public health problem. The long noncoding RNA (lncRNA) mechanisms for dysregulated retinal signaling in the myopic eye have remained elusive. The aim of this study was to analyze the expression profiles and possible pathogenic roles of lncRNAs in mouse form-deprived myopia (FDM) retinas.Methods: A mouse FDM model was induced and retinas from the FDM right eyes and the contralateral eyes were collected for RNA sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and lncRNA-mRNA coexpression network analyses were conducted to explore the biological functions of the differentially expressed lncRNAs. In addition, the levels of differentially expressed lncRNAs in the myopic retinas were validated by quantitative real-time PCR (qRT–PCR). Fluorescence in situ hybridization (FISH) was used to detect the localization of lncRNAs in mouse retinas.Results: FDM eyes exhibited reduced refraction and increased ocular axial length compared to control fellow eyes. RNA sequencing revealed that there were 655 differentially expressed lncRNAs between the FDM and control retinas. Functional enrichment analysis indicated that the differentially expressed RNAs were mostly enriched in cellular processes, cytokine-cytokine receptor interactions, retinol metabolism, and rhythmic processes. Differentially expressed lncRNAs were validated by qRT–PCR. Additionally, RNA FISH showed that XR_384718.4 (Gm35369) localized in the ganglion cell (GCL) and inner nuclear layers (INL).Conclusion: This study identified the differential expression profiles of lncRNAs in myopic mouse retinas. Our results provide scientific evidence for investigations of myopia and the development of putative interventions in the future.

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“…As MIAT also promotes tumorigenesis by binding AEG-1, a protein that affects diverse pathways [ 21 ], it is possible that NFKB signalling is a central lncRNA effector across diseases and tissues. Finally, no clear effector mechanism was defined for OIP5-AS1 during its female-specific cardioprotective role [ 22 ].…”

Section: Functions Of Recently Studied Long Noncoding Rnas In Cardiov...mentioning

confidence: 99%

Long noncoding RNAs in cardiovascular disease

Kohlmaier

Holdt

Teupser

2023

Current Opinion in Cardiology

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Purpose of review Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in lncRNA biology, providing an outlook for future avenues of lncRNA research in CVD. Recent findings Recent publications provide translational evidence from patient studies and animal models for the role of specific lncRNAs in CVD. The molecular effector mechanisms of these lncRNAs are diverse. Overall, cell-type selective modulation of gene expression is the largest common denominator. New methods, such as single-cell profiling and CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many lncRNAs establish RNA-based spatial compartments that concentrate effector proteins. Also, RNA modifications and splicing features can be determinants of lncRNA function. Summary lncRNA research is passing the stage of enumerating lncRNAs or recording simplified on-off expression switches. Mechanistic analyses are starting to reveal overarching principles of how lncRNAs can function. Exploring these principles with decisive genetic testing in vivo remains the ultimate test to discern how lncRNA loci, by RNA motifs or DNA elements, affect CVD pathophysiology.

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Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner

Cited by 16 publications

References 56 publications

Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes

Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes

RNA-sequencing analysis reveals the long noncoding RNA profile in the mouse myopic retina

Long noncoding RNAs in cardiovascular disease

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