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

Luo, Wenjie; Wang, Jun; Xu, Wenhao; Ma, Chao; Wan, Fangning; Huang, Yao Qi; Yao, Mengfei; Zhang, Ye; Qu, Yuanyuan; Ye, Dingwei; Zhu, Yiping

doi:10.1038/s41419-021-04296-1

Cited by 100 publications

(74 citation statements)

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“…LINC00336 suppresses ferroptosis in lung cancer by serving as a ceRNA for miR-6852 [26]. lncRNA RP11-89 suppresses ferroptosis through the miR-129-5p/PROM2 axis and contributes to the advancement of bladder cancer [27]. Recently, several FRL signatures with 3-9 lncRNAs have been constructed for the prognosis of HCC, and the AUC for 3-year OS was 0.649-0.812 [17,[28][29][30][31][32] (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Xiong

Ouyang

Fang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated. Methods. Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson’s correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature’s predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied.Results. In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. Conclusion. The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

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Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Xiong

Ouyang

Fang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Jiang et al found that HELLS interacted with WDR76 (WD repeat domain 76) to inhibit ferroptosis by activating metabolic genes, including glucose transporter 1 (GLUT1), and sterol-CoA desaturase 1 (SCD1), and fatty acid desaturase 2 (FADS2) ( Jiang et al, 2017 ; Mazhar et al, 2021 ). Luo et al revealed that PROM2 promoted iron export and ferroptosis resistance via formation of multivesicular bodies (MVBs) in BLCA ( Luo et al, 2021 ). Li et al demonstrated that carbonic anhydrase 9 (CA9), a classical HIF1A target gene, promoted malignant mesothelioma resistance to ferroptosis and apoptosis under hypoxia ( Li et al, 2019 ; Tang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Tan

Liu

et al. 2022

Front. Pharmacol.

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Pancreatic adenocarcinoma (PAAD) is a malignant cancer with high incidence and mortality. Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of PAAD and contributes to tumorigenesis and progression through numerous mechanisms. This study aimed to identify a novel glycolysis-related lncRNA-miRNA-mRNA ceRNA signature in PAAD and explore its potential molecular function. We first calculated the glycolysis score for each PAAD patient by the ssGSEA algorithm and found that patients with higher hallmark glycolysis scores had poorer prognosis. Subsequently, we obtained a novel glycolysis-related LINC02432/hsa-miR-98–5p/HK2 axis from the TCGA and GEO databases using comprehensive bioinformatics analysis and developed a nomogram to predict overall survival. Furthermore, functional characterization analysis revealed that LINC02432/hsa-miR-98–5p/HK2 axis risk score was negatively correlated with ferroptosis. The tumor immune infiltration analysis suggested positive correlations between ceRNA risk score and infiltrated M0 macrophage levels in PAAD. Correlation analysis found that ceRNA risk scores were positively correlated with four chemokines (CXCL3, CXCL5, CXCL8 and CCL20) and one immune checkpoint gene (SIGLEC15). Meanwhile, tumor mutation burden (TMB), an indicator for predicting response to immunotherapy, was positively correlated with ceRNA risk score. Finally, the drug sensitivity analysis showed that the high-risk score patients might be more sensitive to EGFR, MEK and ERK inhibitors than low-risk score patients. In conclusion, our study suggested that LINC02432/hsa-miR-98–5p/HK2 axis may serve as a novel diagnostic, prognostic, and therapeutic target in PAAD treatment.

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“… lncRNA Role in ferroptosis Mechanism of action Reference P53RRA (LINC00472) Induces ferroptosis in lung cancer Downregulates SCL7A11 [ 38 ] MT1DP Induces ferroptosis in NSCLC Stabilizes miR-365a-3p, downregulates NRF2 [ 113 ] GABPB1-AS1 Induces ferroptosis in HCC Inhibits GABPB1 translation, downregulates GABPB1 and PRDX5 [ 112 ] LINC00618 Induces ferroptosis in leukemias Downregulates SLC7A11 via attenuation of LSH expression [ 37 ] LINC00336 Inhibits ferroptosis in lung cancer Stabilized by ELAVL1 and LSH. Sponges miRNA6852, upregulates CBS [ 114 ] NEAT1 Inhibits ferroptosis in NSCLC Downregulates ACSL4 expression [ 56 ] H19 Inhibits ferroptosis in breast cancer Inhibits production of lipid ROS and induces production of GSH [ 175 ] lncPVT1 Inhibits ferroptosis in HCC Sponges miR-214-3p, upregulates GPX4 [ 29 ] OIP5-AS1 Inhibits ferroptosis in prostate cancer Sponges miR-128-3p, upregulates SLC7A11 expression [ 39 ] RP11-89 Inhibits ferroptosis in bladder cancer Sponges miR-129-5p, upregulates PROM2 which induces iron export [ 176 ] MEG8 Inhibits ferroptosis in benign hemangioma Sponged by miR-497-5p. Upregulates SLC7A11 and GPX4 expression [ 177 ] …”

Section: Introductionmentioning

confidence: 99%

Non-coding RNAs and ferroptosis: potential implications for cancer therapy

et al. 2022

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Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways and molecules are involved in the regulation of ferroptosis, including enzymes that control the cellular redox status. Alterations in the ferroptosis-regulating network can contribute to the development of various diseases, including cancer. Evidence suggests that ferroptosis is commonly suppressed in cancer cells, allowing them to survive and progress. However, cancer cells which are resistant to common chemotherapeutic drugs seem to be highly susceptible to ferroptosis inducers, highlighting the great potential of pharmacologic modulation of ferroptosis for cancer treatment. Non-coding RNAs (ncRNAs) are considered master regulators of various cellular processes, particularly in cancer where they have been implicated in all hallmarks of cancer. Recent work also demonstrated their involvement in the molecular control of ferroptosis. Hence, ncRNA-based therapeutics represent an exciting alternative to modulate ferroptosis for cancer therapy. This review summarizes the ncRNAs implicated in the regulation of ferroptosis in cancer and highlights their underlying molecular mechanisms in the light of potential therapeutic applications.

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

Cited by 100 publications

References 50 publications

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Glycolysis-Related LINC02432/Hsa-miR-98–5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma

Non-coding RNAs and ferroptosis: potential implications for cancer therapy

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