Hypermethylation‐mediated down‐regulation of lncRNA TBX5‐AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing <i>TBX5</i> expression

Ma, Jing; Chen, Shiyu; Hao, Lili; Sheng, Wei; Chen, WeiCheng; Ma, Xiaojing; Zhang, Bowen; Ma, Ding; Huang, Guoying

doi:10.1111/jcmm.15298

Cited by 19 publications

(13 citation statements)

References 60 publications

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“…We found for the first time in CRC that they co-expressed with DEAGs and may be involved in the process of autophagy in CRC. TBX5.AS1 is significantly down-regulated in damaged heart tissue of tetralogy of Fallot ( 40 ). TBX5.AS1 has been found to be a prognostic factor for lung adenocarcinoma ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer

et al. 2021

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Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.

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Section: Discussionmentioning

confidence: 99%

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer

et al. 2021

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“…TBX5-AS1:2 lncRNA regulates Tbx5 expression via modulation of its promoter methylation status. Curiously, TBX5-AS1:2 lncRNA is dysregulated in Tetralogy of Fallot patients, suggesting a plausible role in the onset of this cardiac congenital defect [ 160 ]. Additionally, Tbx5ua , a lncRNA close to Tbx5 locus is required for proper ventricular wall development, and thus being necessary for embryonic development, since Tbx5ua mouse knock-out embryonic lethal [ 161 ] ( Figure 1 A,D) .…”

Section: Post-transcriptional Control Of Heart Fields Deployment By N...mentioning

confidence: 99%

Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis

Lozano-Velasco

García-Padilla

Muñoz-Gallardo

et al. 2022

IJMS

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Cardiovascular development is initiated soon after gastrulation as bilateral precardiac mesoderm is progressively symmetrically determined at both sides of the developing embryo. The precardiac mesoderm subsequently fused at the embryonic midline constituting an embryonic linear heart tube. As development progress, the embryonic heart displays the first sign of left-right asymmetric morphology by the invariably rightward looping of the initial heart tube and prospective embryonic ventricular and atrial chambers emerged. As cardiac development progresses, the atrial and ventricular chambers enlarged and distinct left and right compartments emerge as consequence of the formation of the interatrial and interventricular septa, respectively. The last steps of cardiac morphogenesis are represented by the completion of atrial and ventricular septation, resulting in the configuration of a double circuitry with distinct systemic and pulmonary chambers, each of them with distinct inlets and outlets connections. Over the last decade, our understanding of the contribution of multiple growth factor signaling cascades such as Tgf-beta, Bmp and Wnt signaling as well as of transcriptional regulators to cardiac morphogenesis have greatly enlarged. Recently, a novel layer of complexity has emerged with the discovery of non-coding RNAs, particularly microRNAs and lncRNAs. Herein, we provide a state-of-the-art review of the contribution of non-coding RNAs during cardiac development. microRNAs and lncRNAs have been reported to functional modulate all stages of cardiac morphogenesis, spanning from lateral plate mesoderm formation to outflow tract septation, by modulating major growth factor signaling pathways as well as those transcriptional regulators involved in cardiac development.

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“…On the other hand, it has been demonstrated that the TBX5 gene is modified by different epigenetic mechanisms, including long non-coding RNAs (lncRNAs), histone modification and polycomb group proteins. These epigenetic modifications play a key role in the pathophysiology of CHDs [ 14 , 15 , 16 , 17 ]. Furthermore, some studies have shown that an imbalance in the status of DNA methylation could change the expression of genes that participate in cardiogenesis [ 8 , 10 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients

García-Flores

Rodrı́guez-Pérez

Borgonio-Cuadra

et al. 2022

Biology

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The TBX5 gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). The aim of this research was to evaluate the association between DNA methylation levels of the TBX5 gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the TBX5 gene promoter were evaluated using pyrosequencing analysis in 35 patients with congenital septal defects and 48 controls. Average methylation levels were higher in individuals with congenital septal defects than in the controls (p < 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (p < 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02–14.8; p = 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the TBX5 gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56–0.80; p = 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01–8.33; p = 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the TBX5 gene could be associated with congenital septal defects.

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Hypermethylation‐mediated down‐regulation of lncRNA TBX5‐AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression

Cited by 19 publications

References 60 publications

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer

Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients

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