Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling

Wu, Quansheng; Yin, Xiaofeng; Zhao, Wenbo; Xu, Wenli; Chen, Laizhao

doi:10.1371/journal.pone.0260864

Cited by 15 publications

(11 citation statements)

References 36 publications

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“…We analyzed TOP2A expression in different molecular subtypes of MB based on GEO datasets, and the results revealed that the expression of TOP2A was significantly higher in the WNT and non-WNT/non-SHH groups than in the SHH group. Previous studies have reported that activation of the Wnt/ b-catenin signaling pathway contributes to radioresistance in most tumor types, including glioma, hepatocellular carcinoma, and nasopharyngeal carcinoma (49)(50)(51). However, radiation resistance among the different molecular subtypes of MB has rarely been reported.…”

Section: Discussionmentioning

confidence: 99%

TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma

et al. 2022

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Radiotherapy remains the standard treatment for medulloblastoma (MB), and the radioresistance contributes to tumor recurrence and poor clinical outcomes. Nuclear DNA topoisomerase II-alpha (TOP2A) is a key catalytic enzyme that initiates DNA replication, and studies have shown that TOP2A is closely related to the therapeutic effects of radiation. In this study, we found that TOP2A was significantly upregulated in MB, and high expression of TOP2A related to poor prognosis of MB patients. Knockdown of TOP2A inhibited MB cell proliferation, migration, and invasion, whereas overexpression of TOP2A enhanced the proliferative and invasive ability of MB cells. Moreover, si-TOP2A transfection in combination with irradiation (IR) significantly reduced the tumorigenicity of MB cells, compared with those transfected with si-TOP2A alone. Cell survival curve analysis revealed that the survival fraction of MB cells was significantly reduced upon TOP2A downregulation and that si-TOP2A-transfected cells had decreased D0, Dq, and SF2 values, indicating that TOP2A knockdown suppresses the resistance to radiotherapy in MB cells. In addition, western blot analysis demonstrated that the activity of Wnt/β-catenin signaling pathway was inhibited after TOP2A downregulation alone or in combination with IR treatment, whereas overexpression of TOP2A exhibited the opposite effects. Gene set enrichment analysis also revealed that Wnt/β-catenin signaling pathway is enriched in TOP2A high-expression phenotypes. Collectively, these data indicate that high expression of TOP2A leads to poor prognosis of MB, and downregulation of TOP2A inhibits the malignant behaviour as well as the radioresistance of MB cells. The Wnt/β-catenin signaling pathway may be involved in the molecular mechanisms of TOP2A mediated reduced tumorigenicity and radioresistance of MB cells.

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Section: Discussionmentioning

confidence: 99%

TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma

et al. 2022

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“…rough the activation of Wnt/-catenin signaling, the CRISP/Cas9-mediated reduction of SFRP2 facilitated the development of soft agar colonies, cancer stemness, and radioresistance in glioma cells [33]. Zhang et al reported that when compared to the paired adjacent nontumor tissue, the amount of SFRP2 mRNA in NSCLC tissue was found to be significantly lower, while the amount of SFRP2 gene methylation was found to be significantly higher.…”

Section: Discussionmentioning

confidence: 99%

SFRP2 is a Novel Diagnostic Biomarker and Suppresses the Proliferation of Pituitary Adenoma

Huang

Chen

Wang

et al. 2022

Journal of Oncology

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Pituitary adenoma (PA) constitutes one of the most common intracranial tumors. The present study was designed to identify potential diagnostic markers for PA. We used gene expression profiles (GEO: GSE26966 and GEO: GSE63357 datasets) derived from human PA and nontumor samples that were made freely accessible by the gene expression omnibus (GEO) datasets. Differentially expressed genes (DEGs) were screened between 14 normal specimens and 34 PA specimens by the use of the limma package of the R. The diagnostic genes were determined using a LASSO regression model and SVM-RFE analysis. SFRP2 expression in PA cells was analyzed using RT-PCR, and the effect of SFRP2 dysregulation on PA cell proliferation was measured using CCK-8 analysis. In this study, 361 DEGs were identified: 309 genes were downregulated and 52 genes were upregulated. The results of KEGG assays revealed that the 361 DEGs were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, growth hormone synthesis, secretion and action, and AGE-RAGE signaling pathway in diabetic complications. Results from the LASSO regression model and the SVM-RFE analysis indicated that LOC101060391 and SFRP2 were diagnostic genes. In contrast to normal tissue, the expressions of LOC101060391 and SFRP2 were much lower in PA samples. According to the ROC assays, high LOC101060391 and SFRP2 expression had an AUC value >0.9 for PA. Upregulation of SFRP2 distinctly inhibited the proliferative capacity of PA cells, as shown by CCK-8 analysis. Furthermore, knockdown of SFRP2 had an influence on cell growth in both the AtT-20 and HP75 cell lines. Taken together, our findings indicate that LOC101060391 and SFRP2 have diagnostic potential for PA. Furthermore, SFRP2 may be an antioncogene and a therapeutic target for PA.

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“…A study con rmed for the rst time the role of SFRP2 in the radiation resistance of glioma cells and SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. (24). Li et al indicated that Notch1 can promote invasion, selfrenewal and growth of glioma-initiating cells and is overexpressed in glioma-initiating cells (25).Lan et al con rmed WNT7A is upregulated as a tumor promoter in glioma (26).…”

Section: Discussionmentioning

confidence: 99%

The Stem Cell Division-Related Gene Signature for Risk Stratification and Prognosis of Survival in Lower-Grade

Jiang

Zhu

Yang

et al. 2023

Preprint

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Background: Cancer stem cell genes are proven to be associated with the prognosis of multiple cancers. Nevertheless, the prognosis and role of stem cell division-related genes in lower-grade glioma (LGG) remains unclear. Objective: This study constructs a reliable risk model of stem cell division-related genes for predicting the prognosis of LGG patients. Methods: The mutation data, FPKM data and corresponding clinical information of 511 LGG patients were downloaded from the TCGA database. We carried out LASSO regression analysis and multivariate cox regression analysis to build a risk gene model. The Kaplan-Meier survival analysis was used to evaluate the OS rate of LGG patients. The ROC curve assesses its power across the entire data set. Results: We acquired a total of 30 candidate stem cell division-related genes. Finally, 11 genes were selected (EV12B,ING2, MLLT3, NCOA3, NOTCH1, PRDM15, SFRP2, SMYD5, THOC2, TIAL1 and WNT7A) to construct risk models. We analyzed the genetic alterations of the selected 11 genes in LGG using the cBioPortal database. Mutations were present in all of the 511 patients. The results showed that all query genes were changed in 101 out of 511 cases(19.77%). The 11-gene marker panel was confirmed as an independent prognostic indicators(P<0.001, HR = 1.061, 95% CI = 1.042-1.079). The Kaplan-Meier survival analysis showed that patients with low risk scores survived longer than those with high risk scores.The AUC was 0.827 suggesting that this 11-gene signature played an important role and accuracy in the efficacy of this diagnosis. Conclusion: Our study built a prognostic model consisting of 11 stem cell division-related genes for predicting the prognosis of LGG patients. This may be a new biomarker for predicting LGG. These preliminary findings may provide some useful values for clinical prognosis of LGG and future studies.

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Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling

Cited by 15 publications

References 36 publications

TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma

TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma

SFRP2 is a Novel Diagnostic Biomarker and Suppresses the Proliferation of Pituitary Adenoma

The Stem Cell Division-Related Gene Signature for Risk Stratification and Prognosis of Survival in Lower-Grade

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