ISL2 modulates angiogenesis through transcriptional regulation of ANGPT2 to promote cell proliferation and malignant transformation in oligodendroglioma

Qi, Lin; Wang, Zhong-Yong; Shao, Xin-Rong; Li, Miao; Chen, Shu-Na; Liu, Xue-Qi; Yan, Shi; Zhang, Bo; Zhang, Xudong; Li, Xin; Zhao, Wenxue; Pan, Jing; Zhao, Bo; Zhang, Xingding

doi:10.1038/s41388-020-01411-y

Cited by 17 publications

(21 citation statements)

References 42 publications

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“…In addition, hypoxia acquires the process of carcinogenesis and angiogenesis, which leads to the migration and invasion of glioma cell lines, and angiogenesis significantly worsens prognosis of cancer patients (59)(60)(61)(62). Notably, hypoxia has been shown to promote EMT, which is crucial for malignant progression of tumors (63)(64)(65). Consistent with these studies, the results of GSEA showed that the high-risk group was enriched in the inflammation-related pathways and malignant biological processes such as hypoxia, angiogenesis, and EMT.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of an Mesenchymal-Related Long Non-Coding RNA Prognostic Model in Glioma

et al. 2021

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Glioma is well known as the most aggressive and prevalent primary malignant tumor in the central nervous system. Molecular subtypes and prognosis biomarkers remain a promising research area of gliomas. Notably, the aberrant expression of mesenchymal (MES) subtype related long non-coding RNAs (lncRNAs) is significantly associated with the prognosis of glioma patients. In this study, MES-related genes were obtained from The Cancer Genome Atlas (TCGA) and the Ivy Glioblastoma Atlas Project (Ivy GAP) data sets of glioma, and MES-related lncRNAs were acquired by performing co-expression analysis of these genes. Next, Cox regression analysis was used to establish a prognostic model, that integrated ten MES-related lncRNAs. Glioma patients in TCGA were divided into high-risk and low-risk groups based on the median risk score; compared with the low-risk groups, patients in the high-risk group had shorter survival times. Additionally, we measured the specificity and sensitivity of our model with the ROC curve. Univariate and multivariate Cox analyses showed that the prognostic model was an independent prognostic factor for glioma. To verify the predictive power of these candidate lncRNAs, the corresponding RNA-seq data were downloaded from the Chinese Glioma Genome Atlas (CGGA), and similar results were obtained. Next, we performed the immune cell infiltration profile of patients between two risk groups, and gene set enrichment analysis (GSEA) was performed to detect functional annotation. Finally, the protective factors DGCR10 and HAR1B, and risk factor SNHG18 were selected for functional verification. Knockdown of DGCR10 and HAR1B promoted, whereas knockdown of SNHG18 inhibited the migration and invasion of gliomas. Collectively, we successfully constructed a prognostic model based on a ten MES-related lncRNAs signature, which provides a novel target for predicting the prognosis for glioma patients.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of an Mesenchymal-Related Long Non-Coding RNA Prognostic Model in Glioma

et al. 2021

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“…A heatmap showed that genes related to angiogenesis in the AM_EC group were upregulated compared with those in the AM_EM group, including MMP1 [22], ESM1 [23], ANGPT2 [24] and CYP1B1 [25] (Fig. 3A).…”

Section: Resultsmentioning

confidence: 99%

Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis

Sun

Liu

et al. 2020

Preprint

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Background: Adenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM.Methods: A control endometrium (sample with leiomyoma excluding endometrial disorders, n=1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n=1) samples were analysed by scRNA-seq, and additional leiomyoma (n=3) and adenomyosis (n=3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM.Results: The scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, the epithelial cells transformed to endothelial cells with the obvious accumulation of vasculogenic mimicry formations (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions.Conclusions: In the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.

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“…In recent years, a number of studies have been performed to explore the role of ANGPT2 in cancer (22)(23)(24). For example, miR-145-5p overexpression exerts inhibitory effects on the proliferation, migration and invasion of gastric cancer cells via the ANGPT2 axis (22).…”

Section: Discussionmentioning

confidence: 99%

HOXB5‑activated ANGPT2 promotes the proliferation, migration, invasion and angiogenic effect of esophageal cancer cells via activating ERK/AKT signaling pathway

Gao

2022

Exp Ther Med

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Esophageal cancer, which is the eighth most common cancer worldwide, has a poor prognosis and high mortality rate. The present study was designed to investigate the proliferation, migration, invasion and angiogenic effect of the homeobox B5 (HOXB5)/angiopoietin-2 (ANGPT2) interplay in esophageal cancer. The relative expression of ANGPT2 and HOXB5 in esophageal cancer and the association between gene expression was evaluated using data from Gene Expression Profiling Interactive Analysis databases. Following transduction of short hairpin RNA-ANGPT2#1/2 plasmids, ANGPT2 was silenced. Viability, proliferation and invasion of esophageal cancer cells were assessed using CCK-8, 5-EdU, colony formation, wound healing and Transwell assays, respectively. Moreover, the transcriptional activity of ANGPT2 and angiogenesis were detected with luciferase reporter, chromatin immunoprecipitation (CH-IP) and tube formation assays. The results of the present study indicated that ANGPT2 was upregulated, both in esophageal cancer cell lines and tissue and there was an association between the ANGPT2 upregulation and the poor patient prognosis. In addition, ANGPT2 silencing suppressed esophageal cancer cell proliferation, migration, invasion and angiogenesis. The HOXB5 expression was also increased in esophageal cancer, and transcriptionally activated ANGPT2. Moreover, HOXB5 overexpression reversed the effects of ANGPT2 silencing in esophageal cancer cells. Furthermore, ANGPT2 silencing inactivated ERK/AKT signaling, whereas the HOXB5 overexpression blocked this effect. In conclusion, ANGPT2, which was transcriptionally activated by HOXB5, activated the ERK/AKT signaling pathway to promote proliferation, metastasis and angiogenesis of esophageal cancer cells.

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ISL2 modulates angiogenesis through transcriptional regulation of ANGPT2 to promote cell proliferation and malignant transformation in oligodendroglioma

Cited by 17 publications

References 42 publications

Development and Validation of an Mesenchymal-Related Long Non-Coding RNA Prognostic Model in Glioma

Development and Validation of an Mesenchymal-Related Long Non-Coding RNA Prognostic Model in Glioma

Single-cell Transcriptomic Analysis of Eutopic Endometrium and Ectopic Lesions of Adenomyosis

HOXB5‑activated ANGPT2 promotes the proliferation, migration, invasion and angiogenic effect of esophageal cancer cells via activating ERK/AKT signaling pathway

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