Androgen Receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM) <i>via</i> altering TWIST1 nonsense-mediated decay through lncRNA-TANAR

You, Bosen; Sun, Yin; Liu, Qing; Wang, Keliang; Fang, Ruizhe; Liu, Bingmei; Chou, Fu-Ju; Luo, Jie; Wang, Ronghao; Meng, Jialin; Huang, Chi‐Ping; Yeh, Shuyuan; Xu, Wanhai; Chang, Chawnshang

doi:10.1101/2020.06.30.180067

Cited by 4 publications

(4 citation statements)

References 56 publications

(58 reference statements)

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“…A preclinical study using a in vivo mouse model with orthotopic xenografts of clear cell renal cell carcinoma cells further confirmed the in vitro data. These results illustrated that AR-mediated TANAR signals might play a crucial role in clear cell renal cell carcinoma VM formation and metastasis, and targeting this newly identified AR/TANAR/TWIST1 signaling may help in the development of a novel anti-angiogenesis therapy to better suppress the clear cell renal cell carcinoma progression ( You et al, 2021 ). We analyzed differences in the expression of EMT-related genes between the two risk groups, and the results were consistent with expectations ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 94%

Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma

Shen

Wang

et al. 2021

Front. Cell Dev. Biol.

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BackgroundLung adenocarcinoma (LUAD) originates mainly from the mucous epithelium and glandular epithelium of the bronchi. It is the most common pathologic subtype of non-small cell lung cancer (NSCLC). At present, there is still a lack of clear criteria to predict the efficacy of immunotherapy. The 5-year survival rate for LUAD patients remains low.MethodsAll data were downloaded from The Cancer Genome Atlas (TCGA) database. We used Gene Set Enrichment Analysis (GSEA) database to obtain immune-related mRNAs. Immune-related lncRNAs were acquired by using the correlation test of the immune-related genes with R version 3.6.3 (Pearson correlation coefficient cor = 0.5, P < 0.05). The TCGA-LUAD dataset was divided into the testing set and the training set randomly. Based on the training set to perform univariate and multivariate Cox regression analyses, we screened prognostic immune-related lncRNAs and given a risk score to each sample. Samples were divided into the high-risk group and the low-risk group according to the median risk score. By the combination of Kaplan–Meier (KM) survival curve, the receiver operating characteristic (ROC) (AUC) curve, the independent risk factor analysis, and the clinical data of the samples, we assessed the accuracy of the risk model. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differentially expressed mRNAs between the high-risk group and the low-risk group. The differentially expressed genes related to immune response between two risk groups were analyzed to evaluate the role of the model in predicting the efficacy and effects of immunotherapy. In order to explain the internal mechanism of the risk model in predicting the efficacy of immunotherapy, we analyzed the differentially expressed genes related to epithelial-mesenchymal transition (EMT) between two risk groups. We extracted RNA from normal bronchial epithelial cell and LUAD cells and verified the expression level of lncRNAs in the risk model by a quantitative real-time polymerase chain reaction (qRT-PCR) test. We compared our risk model with other published prognostic signatures with data from an independent cohort. We transfected LUAD cell with siRNA-LINC0253. Western blot analysis was performed to observed change of EMT-related marker in protein level.ResultsThrough univariate Cox regression analysis, 24 immune-related lncRNAs were found to be strongly associated with the survival of the TCGA-LUAD dataset. Utilizing multivariate Cox regression analysis, 10 lncRNAs were selected to establish the risk model. The K-M survival curves and the ROC (AUC) curves proved that the risk model has a fine predictive effect. The GO enrichment analysis indicated that the effect of the differentially expressed genes between high-risk and low-risk groups is mainly involved in immune response and intercellular interaction. The KEGG enrichment analysis indicated that the differentially expressed genes between high-risk and low-risk groups are mainly involved in endocytosis and the MAPK signaling pathway. The expression of genes related to the efficacy of immunotherapy was significantly different between the two groups. A qRT-PCR test verified the expression level of lncRNAs in LUAD cells in the risk model. The AUC of ROC of 5 years in the independent validation dataset showed that this model had superior accuracy. Western blot analysis verified the change of EMT-related marker in protein level.ConclusionThe immune lncRNA risk model established by us could better predict the prognosis of patients with LUAD.

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Section: Discussionmentioning

confidence: 94%

Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma

Shen

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…The enhanced expression of the androgen receptor (AR) is associated with tumor angiogenesis. AR stimulates the creation of angiogenic mimics in ccRCC cells by modulating the lncRNA TANAR/TWIST1 pathway, according to in vitro studies [35]. By inhibiting angiogenesis, the AR/TANA/TWIST1 pathway can slow the advancement of ccRCC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of M6A-Related lncRNAs, Immune Checkpoints and Immune Infiltrates in Clear Cell Renal Cell Carcinoma

Lin

Zhang

Guo

et al. 2022

Preprint

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Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in the world and is strongly related to the tumor immune microenvironment (TIME), which is mediated by N6 Methyladenosine-related long noncoding RNAs (m6A-related lncRNAs). In order to explore the underlying effective treatment and prognostic biomarkers, the correlation of m6A-related lncRNA, TIME with survival deserves in-depth study. Methods All the data which include 53 tumor samples as well as 72 normal samples were obtained from The Cancer Genome Atlas (TCGA). Herein, we systematically explored the correlations of prominent m6A-related lncRNAs with 5 immune checkpoints (CTLA4, TIGIT, PDCD1, CD19 and LAG3) and immune infiltrates. Patients were divided into 2 clusters based on 30 prognostic m6A-related lncRNAs. Six m6A-related lncRNA-associated signatures were used to construct a risk model for ccRCC. Following that, we investigated the correlation between m6A-related lncRNA-associated signatures and immune cells, immune score, and immune checkpoints. Results The expressions of these 5 immune checkpoints (CTLA4, TIGIT, PDCD1, CD19 and LAG3) were positively correlated with the expressions of the 30 m6A-related lncRNAs. Compared to cluster 1, cluster 2 had a higher immunoscore, remarkable immune cell infiltration, upregulated checkpoints and poor prognosis. The hallmarks protein secret, androgen response, adipogenesis, bile acid metabolism, fatty acid metabolism and PPAR signaling pathway were remarkably enriched in the cluster 1. With high-risk scores, patients had higher immunoscore and higher expression of the 5 immune checkpoints. The amount of tumor-infiltrating immune cells was dynamically altered by copy-number changes in m6A-related lncRNA-associated signatures. Conclusions Our research revealed the crucial involvement of m6A-related lncRNAs in the TIME of ccRCC. The suggested m6A-related lncRNA-associated signatures might be important mediators of TIME in ccRCC, providing ideal therapeutic targets in immunotherapeutic effectiveness.

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“…Vasculogenic mimicry (VM) was identified through the detection of CD31–negative and PAS‐positive lumen–like structures surrounded by tumour cells (but not with endothelial cells) with or without red blood cells inside the lumen 28–32 (Figure 1A). The vascular structures were observed for structural integrity with no incidence of haemorrhage, necrosis or inflammatory cell infiltration in close proximity 33–36 .…”

Section: Methodsmentioning

confidence: 99%

Orchestrated expression of vasculogenic mimicry and laminin‐5γ2 is an independent prognostic marker in oral squamous cell carcinoma

Saha

Mitra

Alam

et al. 2022

Int J Experimental Path

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Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC.

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Androgen Receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM) via altering TWIST1 nonsense-mediated decay through lncRNA-TANAR

Cited by 4 publications

References 56 publications

Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma

Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma

Comprehensive Analysis of M6A-Related lncRNAs, Immune Checkpoints and Immune Infiltrates in Clear Cell Renal Cell Carcinoma

Orchestrated expression of vasculogenic mimicry and laminin‐5γ2 is an independent prognostic marker in oral squamous cell carcinoma

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