Intravesical <i>In Situ</i> Immunostimulatory Gel for Triple Therapy of Bladder Cancer

Guo, Pengyu; Wang, Lu; Shang, Wenting; Chen, Jiuwei; Chen, Ziyin; Xiong, Feng; Wang, Ziqi; Tong, Zheming; Wang, Keliang; Yang, Liming; Hui, Hui; Xu, Wanhai

doi:10.1021/acsami.0c15176

Cited by 53 publications

(35 citation statements)

References 30 publications

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“…In addition, recent studies have shown that ferroptosis strategy is sensitive to bladder cancer. For example, a novel agent called AuNRs&IONs@Gel constructed by Pengyu Guo was reported to induce ferroptosis and trigger a potent immune response through a triple therapy strategy using FDA-approved nanoparticles in BLCA [ 39 ]. The relationship between immune statue and ferroptosis in BLCA has been explored by accumulating studies [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

et al. 2021

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Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

et al. 2021

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“…A pan-cancer analysis on the association of CALU with HSPA5, GPX4 and SLC7A11 further confirmed the potential involvement of CALU in the regulation of ferroptosis. Although research on ferroptosis was limited in BLCA, a recent study has demonstrated that a biogel system combining photothermal, ferroptotic, and immune therapy through intravesical instillation effectively inhibits BLCA progression ( 43 ). These results indicated the potential involvement of CALU in the ferroptosis process and enhanced the application significance of ferroptosis-related therapy in BLCA treatments.…”

Section: Discussionmentioning

confidence: 99%

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

Miao

Jiang

et al. 2021

Front. Oncol.

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The tumor microenvironment (TME) plays a critical regulatory role in bladder cancer (BLCA) progression and metastasis. Epithelial-mesenchymal transition (EMT) presents as an essential mechanism of tumor invasion and metastasis. Accumulating pieces of evidence indicated that several microenvironmental factors, including fibroblasts, endothelial, and immune cells, induced EMT in tumor cells. As a hallmark gene of the EMT process, calumenin (CALU) was previously reported to directly impact cancer metastasis. However, the functions and molecular mechanisms of CALU have been rarely reported in BLCA. By multi-omics bioinformatics analysis of 408 TCGA BLCA patients, we demonstrated that CALU was an independent risk factor for BLCA outcome. Subsequently, we verified the correlation of CALU with cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells. The results suggested a positive correlation of CALU with CAFs, CD8+ T cells and macrophages. Also, CALU was significantly associated with multiple immune checkpoint-related genes, which ultimately influenced patients’ responsiveness to immunotherapy. Further, we found that the impact of CALU on BLCA prognosis might also be correlated with gene mutations and ferroptosis. Finally, we validated the roles of CALU by single-cell RNA sequencing, PCR and immunohistochemistry. In conclusion, we found that CALU affected BLCA prognosis associated with multiple mechanisms, including TME remodeling, gene mutation and ferroptosis. Further studies on CALU may provide new targets for BLCA immunotherapy and precision medicine.

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“…MIBC generally has poor prognoses and high recurrence rates after the first resection. Several studies have suggested that a complex molecular biological link exists between bladder cancer cell proliferation and iron ions (24,25). However, at the present time, the exact relationship between ferroptosis and bladder cancer has not been reported in detail.…”

Section: Discussionmentioning

confidence: 79%

A Novel Ferroptosis-Related Gene Model for Overall Survival Predictions of Bladder Urothelial Carcinoma Patients

Zhang

Zhang²,

Yu³

et al. 2021

Front. Oncol.

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IntroductionBladder cancer is the most common urinary tract malignancy, and 90% of bladder tumors are urothelial cell carcinomas. Ferroptosis is a new form of cell death discovered in recent years, which is an iron-dependent form of cell death characterized by the lethal intracellular accumulation of lipid-based reactive oxygen species. Ferroptosis is considered to be a double-edged sword for cancer and cancer therapy.Materials and MethodsIn the current study, expression profiles of bladder cancer (BLCA) specimens were obtained from The Cancer Genome Atlas (TCGA) RNA-Seq database. Ferroptosis-related genes were downloaded from the FerrDb website. The ferroptosis-related differentially expressed genes (DEGs) which were related to overall survival (OS) were first identified. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression methods were utilized to develop a ferroptosis-related prognostic model (FRPM). In addition, a nomogram model based on FRPM and clinicopathological features was successfully constructed and validated. In addition, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) methods were utilized in this study in order to compare the DEGs between the high-risk and low-risk groups. This study also adopted RT-qPCR, CCK-8 assay, and scratch assay methods to perform experimental verification processes.Results and DiscussionA 7-gene FRPM was constructed in this research investigation in order to stratify the patients into two groups according to their risk scores. The results of this study’s survival analysis and time-dependent receiver operating characteristic (ROC) analysis demonstrated that the model had achieved a stable performance level. This multivariate Cox regression results revealed that the FRPM was an independent prognostic predictor for the OS of BLCA patients and the results were displayed using a nomogram. In addition, the ROC analysis, concordance index (C-index), calibration plots, and decision curve analysis (DCA) curves further indicated that this study’s nomogram method enabled valuable prediction results. The functional enrichment analysis results suggested that the DEGs between the high- and low-risk groups played vital roles in the progression of the ferroptosis. Also, the ssGSEA indicated that the immune status was different between the two groups. This study found that the RT-qPCR results had confirmed the differential expressions of DEGs in the tissue samples, and the CCK-8 assay and scratch assay results confirmed the promoting effects of SCD on the proliferation and migration of tumor cells.ConclusionsThis study defined a novel prognostic model of seven ferroptosis-related genes, which proved to be independently associated with the OS of BLCA. A nomogram method was developed for the purpose of providing further insight into the accurate predictions of BLCA prognoses.

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Intravesical In Situ Immunostimulatory Gel for Triple Therapy of Bladder Cancer

Cited by 53 publications

References 30 publications

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

The Epithelial to Mesenchymal Transition Related Gene Calumenin Is an Adverse Prognostic Factor of Bladder Cancer Correlated With Tumor Microenvironment Remodeling, Gene Mutation, and Ferroptosis

A Novel Ferroptosis-Related Gene Model for Overall Survival Predictions of Bladder Urothelial Carcinoma Patients

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