Long Non-coding RNA MIAT Knockdown Prevents the Formation of Intracranial Aneurysm by Downregulating ENC1 via MYC

Li, Xinguo; Zhao, Hang; Liu, Jihui; Tong, Jing

doi:10.3389/fphys.2020.572605

Cited by 10 publications

(8 citation statements)

References 34 publications

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“… Jayasooriya et al (2018) found that camptothecin enhanced MYC-mediated ERS and led to autophagy. In addition, Li et al (2020) proved that the downregulating MYC-mediated ENC1 could prevent IA formation. Correlation analysis showed the tight connectivity between ERS signature genes and nearby genes of regulatory regions.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Chen

Zhou

et al. 2022

Front. Cell. Neurosci.

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BackgroundAberrant endoplasmic reticulum stress (ERS) plays an important role in multiple cardiovascular diseases. However, their implication in intracranial aneurysms (IAs) remains unclear. We designed this study to explore the general expression pattern and potential functions of ERS in IAs.MethodsFive Gene Expression Omnibus (GEO) microarray datasets were used as the training cohorts, and 3 GEO RNA sequencing (RNA-seq) datasets were used as the validating cohorts. Differentially expressed genes (DEGs), functional enrichment, Lasso regression, logistic regression, ROC analysis, immune cell profiling, vascular smooth muscle cell (VSMC) phenotyping, weighted gene coexpression network analysis (WGCNA), and protein-protein interaction (PPI) analysis were applied to investigate the role of ERS in IA. Finally, we predicted the upstream transcription factor (TF)/miRNA and potential drugs targeting ERS.ResultsSignificant DEGs were majorly associated with ERS, autophagy, and metabolism. Eight-gene ERS signature and IRE1 pathway were identified during the IA formation. WGCNA showed that ERS was highly associated with a VSMC synthesis phenotype. Next, ERS-VSMC-metabolism-autophagy PPI and ERS-TF-miRNA networks were constructed. Finally, we predicted 9 potential drugs targeting ERS in IAs.ConclusionERS is involved in IA formation. Upstream and downstream regulatory networks for ERS were identified in IAs. Novel potential drugs targeting ERS were also proposed, which may delay IA formation and progress.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Chen

Zhou

et al. 2022

Front. Cell. Neurosci.

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“…Previously, accumulated studies have documented many molecules involved in IA, such as long noncoding RNA myocardial infarction associated transcript (MIAT), 25 stromal cell-derived factor-1alpha (SDF-1α), 26 histone deacetylase 9 (HADC9), 27 and coenzyme Q10. 28 Using an IA-related microarray, we provided new insights into YAP1-dependent functions in IA.…”

Section: Discussionmentioning

confidence: 99%

Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm

Yan,

Qin,

Zheng

et al. 2024

Vasc Med

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Introduction: Intracranial aneurysm (IA) is a common vascular enlargement that occurs in the wall of cerebral vessels and frequently leads to fatal subarachnoid hemorrhage. PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein that functions as a platform for multiple protein complex formation. However, whether PDLIM is involved in the pathogenesis of IA remains poorly understood. Methods: Loss-of-function and gain-of-function strategies were employed to determine the in vitro roles of PDLIM1 in vascular endothelial cells (VECs). A rat model of IA was generated to study the role of PDLIM1 in vivo. Gene expression profiling, Western blotting, and dual luciferase reporter assays were performed to uncover the underlying cellular mechanism. Clinical IA samples were used to determine the expression of PDLIM1 and its downstream signaling molecules. Results: PDLIM1 expression was reduced in the endothelial cells of IA and was regulated by Yes-associated protein 1 (YAP1). Genetic silencing of PDLIM1 inhibited the viability, migratory ability, and tube formation ability of VECs. Opposite results were obtained by ectopic expression of PDLIM1. Additionally, PDLIM1 overexpression mitigated IA in vivo. Mechanistic investigations revealed that PDLIM1 promoted the transcriptional activity of β-catenin and induced the expression of v-myc myelocytomatosis viral oncogene homolog (MYC) and cyclin D1 (CCND1). In clinical settings, reduced expression of PDLIM1 and β-catenin downstream target genes was observed in human IA samples. Conclusion: Our study indicates that YAP1-dependent expression of PDLIM1 can inhibit IA development by modulating the activity of the Wnt/β-catenin signaling pathway and that PDLIM1 deficiency in VECs may represent a potential marker of aggressive disease.

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“…Notably, we found significantly lower MIAT expression levels in MYC-translocated patients, and, accordingly, we found a significant enrichment of MYC targets in MM cases expressing MIAT at lower levels, thus suggesting a possible relationship between MIAT and MYC in MM. Studies in solid tumors [ 30 , 31 , 32 ] and other pathological conditions [ 33 , 34 ] have already described an interplay between MIAT and MYC family genes based on different regulation mechanisms, suggesting that this relationship may depend on the cellular context. Further studies are needed to clarify the relationship in MM.…”

Section: Discussionmentioning

confidence: 99%

Dissecting the Biological Relevance and Clinical Impact of lncRNA MIAT in Multiple Myeloma

Todoerti

Ronchetti

Puccio

et al. 2021

Cancers

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The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an essential aspect of the investigation, which may contribute to understanding the disease’s complex pathobiology, providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the clinical relevance of the lncRNA MIAT in MM, taking advantage of the publicly available CoMMpass database. MIAT expression in MM is highly heterogeneous and significantly associated with specific molecular lesions frequently occurring in MM. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of MIAT in different signaling pathways and ribosome biogenesis and assembly. These findings suggest that MIAT deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and, indirectly, the translational process. Although MIAT expression levels seem not to be significantly associated with clinical outcome in multivariate analyses, high MIAT expression levels are associated with bortezomib resistance, this suggesting that MIAT targeting could overcome drug resistance in MM. These findings strongly prompt for further studies investigating the significance of MIAT in MM.

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Long Non-coding RNA MIAT Knockdown Prevents the Formation of Intracranial Aneurysm by Downregulating ENC1 via MYC

Cited by 10 publications

References 34 publications

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Comprehensive Analysis of Endoplasmic Reticulum Stress in Intracranial Aneurysm

Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm

Dissecting the Biological Relevance and Clinical Impact of lncRNA MIAT in Multiple Myeloma

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