Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc

Bian, Erbao; Chen, Xueran; Cheng, Li; Cheng, Meng; Chen, Zhigang; Yue, Xiaoyu; Zhang, Zhengwei; Chen, Jie; Sun, Libo; Huang, Kebing; Huang, Cheng; Fang, Zhiyou; Zhao, Bing; Li, Jun

doi:10.1186/s13046-021-02129-9

Cited by 30 publications

(34 citation statements)

References 66 publications

(38 reference statements)

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“…Studies have shown that in many human malignancies, including glioma, functional alterations of specific lncRNAs promote tumor formation, progression, and metastasis ( 30 ). Previously, our study found that the activation of lncRNA TMEM44-AS1 can promote malignant progression of glioma through Myc positive feedback loop ( 31 ). Tumor cells often grow in an anoxic environment with chronic ER stress, which is caused by the accumulation of misfolded and unfolded proteins in the ER under various stimuli and pathological conditions ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 97%

A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

Zheng

Yue²,

Fang³

et al. 2022

Front. Oncol.

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Gliomas are a group of the most aggressive primary central nervous system tumors with limited treatment options. The abnormal expression of long non-coding RNA (lncRNA) is related to the prognosis of glioma. However, the role of endoplasmic reticulum (ER) stress-associated lncRNAs in glioma prognosis has not been reported. In this paper, we obtained ER stress-related lncRNAs by co-expression analysis, and then a risk signature composed of 6 ER stress-related lncRNAs was constructed using Cox regression analysis. Glioma samples in The Cancer Genome Atlas (TCGA) were separated into high- and low-risk groups based on the median risk score. Compared with the low-risk group, patients in the high-risk group had shorter survival times. Additionally, we verified the predictive ability of these candidate lncRNAs in the testing set. Three glioma patient subgroups (cluster 1/2/3) were identified by consensus clustering. We further analysed the abundance of immune-infiltrating cells and the expression levels of immune checkpoint molecules in both three subgroups and two risk groups, respectively. Immunotherapy and anticancer drug response prediction showed that ER stress-related lncRNA risk signature positively correlates with responding to immune checkpoints and chemosensitivity. Functional analysis showed that these gene sets are enriched in the malignant process of tumors. Finally, LINC00519 was chosen for functional experiments. The silence of LINC00519 restrained the migration and invasion of glioma cells. Hence, those results indicated that ER stress-related lncRNA risk signature could be a potential treatment target and a prognosis biomarker for glioma patients.

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Section: Discussionmentioning

confidence: 97%

A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

Zheng

Yue²,

Fang³

et al. 2022

Front. Oncol.

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“…Oncogenic super-enhancers were also identified in colorectal cancer through genome-wide profiling [ 18 ]. In addition, super-enhancer was reported to play a role in glioma progression [ 19 ]. Super-enhancer was also found to be involved in squamous cell carcinoma [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Super-enhancers were found to govern PHF19 and TBC1D16 and participate in colorectal cancer tumorigenesis. In addition, super-enhancer was reported to play a role in glioma progression [ 19 ]. In glioma cells, TMEM44-AS1 activates Myc signaling, and Myc binds to the super-enhancer of TMEM44-AS1, forming a positive feedback loop.…”

Section: Introductionmentioning

confidence: 99%

Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia

Fang

Lü

Sang

et al. 2022

J Exp Clin Cancer Res

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Background Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. Methods ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Results We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. Conclusions In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.

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“…(stimulating tumor cell proliferation, colony formation, migration and invasion [15] ) and mRNA SERPINB2…”

Section: Discussionmentioning

confidence: 99%

Analysis of differentially expressed genes between paroxysmal and persistent atrial fibrillation

Ning

Wang

et al. 2022

Preprint

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Background This study aims to analyze the differentially expressed long noncoding RNAs and messenger RNAs (DELncRNAs and DEmRNAs) in patients with paroxysmal and persistent atrial fibrillation and explore the novel AF-related molecular mechanisms.Methods Two target datasets about paroxysmal and persistent atrial fibrillation patients (GSE75092 and GSE113013) were downloaded and further analyzed from the Gene Expression Omnibus database by R software. Upregulated and downregulated differentially expressed genes (DEGs) and the co-expressed differentially expressed genes (co-DEGs) of the two datasets were identified, of which enrichment analyses and protein-protein interaction network construction were performed. Results A total of 127 DELncRNAs and 321 DEmRNAs were screened in GSE75092; a total of 46 DELncRNAs and 64 DEmRNAs were screened in GSE113013. 8 co-DEGs were further identified in the overlap between the two datasets on Venn Diagram, which comprises 3 LncRNA and 5 mRNA. GO and KEGG analysis were successfully performed on the DEGs and co-DEGs mentioned above and the protein-protein interaction network of DEGs was constructed.Conclusions Multiple DEGs were found in patients with either paroxysmal or persistent atrial fibrillation and their functions were mainly enriched in metabolism and inflammation-related signaling pathways. The antiviral defense mechanism of PAF is an interesting difference we found.

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Super-enhancer-associated TMEM44-AS1 aggravated glioma progression by forming a positive feedback loop with Myc

Cited by 30 publications

References 66 publications

A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia

Analysis of differentially expressed genes between paroxysmal and persistent atrial fibrillation

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