Downregulated ESRP1/2 promotes lung metastasis of bladder carcinoma through altering FGFR2 splicing and macrophage polarization

Zhao, Yuyang; Li, Mingyang; Wu, Wenbo; Miao, Wenhao; Liu, Haitao

doi:10.3389/fimmu.2023.1161273

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…A study has shown that AS is connected with the proliferation and invasion of cancer cells ( 19 ). Different types of ASEs and polarization of macrophages can promote metastasis of lung cancer ( 20 ). High expression of COLIA1 can promote the proliferation and metastasis of cervical cancer cells ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma

Zhao,

He,

Liu

et al. 2024

J Thorac Dis

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Background As a post-transcriptional regulatory mechanism, alternative splicing (AS) is engaged in a variety of pathophysiological processes, and it has been widely reported in connection with the occurrence, progression, metastasis, and drug resistance of cancer. However, the research on AS in lung adenocarcinoma (LUAD) is very limited. In addition, the prognostic effect of AS event (ASE) on LUAD and its related mechanism are not clear. This study aimed to explore the role and potential prognostic value of ASE in LUAD. Methods Relevant data and ASE datasets of the sample were acquired from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. We constructed a new prognostic criterion based on ASEs. Then, Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the model. Based on this model, the risk score of each ASE was calculated, and the reliability of this model was evaluated by Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses. Finally, these results were verified on different network platforms. Results We identified seven types of ASEs related to survival. The prognostic risk model for ASEs was established. The Kaplan-Meier curve showed that compared to the low-risk group, the overall survival (OS) rate of LUAD patients in the high-risk group was lower. ROC curve analysis showed that the prognostic risk model of LUAD patients was well predicted, and the area under the curve (AUC) also confirmed this. Conclusions This study screened the ASE related to the prognosis of LUAD patients, and provided a theoretical basis for further study of the correlation between ASE and the prognosis of LUAD patients. It has provided new ideas for developing new biomarkers and therapeutic targets for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma

Zhao,

He,

Liu

et al. 2024

J Thorac Dis

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“…High ESRP2 expression associated with lymph node metastasis ( p < 0.0001) has been reported in prostate cancer [ 64 ]. In bladder cancer, a high level of ESRP2 expression has been linked to lung metastasis ( p < 0.0001) [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel

Hwang,

Bang,

Choi

et al. 2024

Cancers

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Purpose: Papillary renal cell carcinoma (PRCC), the second most common kidney cancer, is morphologically, genetically, and molecularly heterogeneous with diverse clinical manifestations. Genetic variations of PRCC and their association with survival are not yet well-understood. This study aimed to identify and validate survival-specific genes in PRCC and explore their clinical utility. Materials and Methods: Using machine learning, 293 patients from the Cancer Genome Atlas-Kidney Renal Papillary Cell Carcinoma (TCGA-KIRP) database were analyzed to derive genes associated with survival. To validate these genes, DNAs were extracted from the tissues of 60 Korean PRCC patients. Next generation sequencing was conducted using a customized PRCC gene panel of 202 genes, including 171 survival-specific genes. Kaplan–Meier and Log-rank tests were used for survival analysis. Fisher’s exact test was performed to assess the clinical utility of variant genes. Results: A total of 40 survival-specific genes were identified in the TCGA-KIRP database through machine learning and statistical analysis. Of them, 10 (BAP1, BRAF, CFDP1, EGFR, ITM2B, JAK1, NODAL, PCSK2, SPATA13, and SYT5) were validated in the Korean-KIRP database. Among these survival gene signatures, three genes (BAP1, PCSK2, and SPATA13) showed survival specificity in both overall survival (OS) (p = 0.00004, p = 1.38 × 10−7, and p = 0.026, respectively) and disease-free survival (DFS) (p = 0.00002, p = 1.21 × 10−7, and p = 0.036, respectively). Notably, the PCSK2 mutation demonstrated survival specificity uniquely in both the TCGA-KIRP (OS: p = 0.010 and DFS: p = 0.301) and Korean-KIRP (OS: p = 1.38 × 10−7 and DFS: p = 1.21 × 10−7) databases. Conclusions: We discovered and verified genes specific for the survival of PRCC patients in the TCGA-KIRP and Korean-KIRP databases. The survival gene signature, including PCSK2 commonly obtained from the 40 gene signature of TCGA and the 10 gene signature of the Korean database, is expected to provide insight into predicting the survival of PRCC patients and developing new treatment.

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“…In this study, ESRP1 was found to decrease the migration and invasion of gastric cancer cells, suggesting the tumor-suppressive role of ESRP1. Furthermore, ESRP1 reduction promoted tumor growth and lung metastasis of bladder cancer in vivo [ 18 ]. However, the prognostic significance and role of ESRP1 in bladder, cervical, gastric, and renal cancers are unclear and need to be further investigated.…”

Section: Dual Role Of Esrp1 In Cancer Progressionmentioning

confidence: 99%

“…Another study reported the effect of ESRP1 on tumor-associated macrophages in the TME. ESRP1 inhibited tumor growth and lung metastasis in xenograft mouse model of bladder cancer, and also promoted the polarization of tumor-associated macrophages into anti-tumor phenotype in vivo [ 18 ]. This suggests that ESRP1 plays a tumor-suppressive role in bladder cancer in part by its effect on macrophage polarization.…”

Section: Emerging Roles Of Esrp1 In Cancermentioning

confidence: 99%

“…Consistent with the involvement of ESRP1 in the EMT, previous studies have reported the prognostic significance and role of ESRP1 in tumor progression. While ESRP1 has been frequently reported as a tumor suppressor in various cancers [ 15 – 18 ], its pro-tumorigenic role has also been shown in some cancers, such as breast and ovarian cancers [ 13 , 14 , 19 , 20 ], indicating that ESRP1 plays a dual role in cancer progression depending on the cancer type. Furthermore, recent studies have demonstrated that ESRP1 is involved in non-EMT processes, thus contributing to cancer progression.…”

Section: Introductionmentioning

confidence: 99%

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Role of epithelial splicing regulatory protein 1 in cancer progression

Kwon

2023

Cancer Cell Int

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As aberrant alternative splicing by either dysregulation or mutations of splicing factors contributes to cancer initiation and progression, splicing factors are emerging as potential therapeutic targets for cancer therapy. Therefore, pharmacological modulators targeting splicing factors have been under development. Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific splicing factor, whose downregulation is associated with epithelial–mesenchymal transition (EMT) by regulating alternative splicing of multiple genes, such as CD44, CTNND1, ENAH, and FGFR2. Consistent with the downregulation of ESRP1 during EMT, it has been initially revealed that high ESRP1 expression is associated with favorable prognosis and ESRP1 plays a tumor-suppressive role in cancer progression. However, ESRP1 has been found to promote cancer progression in some cancers, such as breast and ovarian cancers, indicating that it plays a dual role in cancer progression depending on the type of cancer. Furthermore, recent studies have reported that ESRP1 affects tumor growth by regulating the metabolism of tumor cells or immune cell infiltration in the tumor microenvironment, suggesting the novel roles of ESRP1 in addition to EMT. ESRP1 expression was also associated with response to anticancer drugs. This review describes current understanding of the roles and mechanisms of ESRP1 in cancer progression, and further discusses the emerging novel roles of ESRP1 in cancer and recent attempts to target splicing factors for cancer therapy.

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Downregulated ESRP1/2 promotes lung metastasis of bladder carcinoma through altering FGFR2 splicing and macrophage polarization

Cited by 6 publications

References 26 publications

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma

Discovery and Validation of Survival-Specific Genes in Papillary Renal Cell Carcinoma Using a Customized Next-Generation Sequencing Gene Panel

Role of epithelial splicing regulatory protein 1 in cancer progression

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