Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis

Xu, Xiequn; Zhang, Xiyang; Wei, Chengqiong; Zheng, Dongxuan; Lü, Xi; Yang, Yingying; Luo, Ailin; Zhang, Kefeng; Duan, Xiaoqun; Wang, Yuhui

doi:10.1016/j.ejps.2020.105450

Cited by 113 publications

(84 citation statements)

References 35 publications

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“…Regulate ferroptosis in tumor cells is a novel treatment modality [5]. Increasing evidence supports that ferroptosis participates in the pathophysiology of COAD [6][7][8]. Thus, identifying critical regulators of ferroptosis is an essential step towards a more in-depth understanding.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer

Cheng

Zhuang

et al. 2021

Bosn J of Basic Med Sci

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Ferroptosis is a form of iron-dependent programmed cell death. Regulate ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan–Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P<0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P<0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.

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Section: Introductionmentioning

confidence: 99%

Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer

Cheng

Zhuang

et al. 2021

Bosn J of Basic Med Sci

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“…Cystine in the cells is further reduced to cysteine, which is an essential precursor required for GSH synthesis. Ferroptosis can be initiated by depletion of cellular cysteine through inhibition of cystine uptake mediated by SLC7A11 [29,30]. Previous results showed that SLC7A11 downregulation signi cantly increased the susceptibility to ferroptosis in nascent neoplastic cells, thus keeping tumorigenesis in check.…”

Section: Discussionmentioning

confidence: 99%

Environmental Allergens House Dust Mites-induced Asthma Causes Ferroptosis in the Lungs

Tang

Dong

Teng

et al. 2021

Preprint

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Background: Studies have indicated that allergens such as house dust mites (HDM) in the environment could induce allergic asthma. Ferroptosis is a newly discovered regulatory cell death characterized by aberrant lipid peroxidation and accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological progress of asthma remains to be elucidated. In this study, we used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and the underlying mechanisms. Methods: Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation and mucus secretion, IgE and cytokine levels as well as inflammatory cell counts in bronchalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mitochondria, ROS, glutathione (GSH) levels and changes in ferroptosis pathway proteins in the lung were also determined. Results: HDM exposure increased AHR significantly, and enhanced inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE level in BALF, lung eosinophilia, and a concomitant increase in IL-13 and IL-5 in BALF were observed. HDM inhalation increased ROS and decreased GSH level in the lung. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blot analysis demonstrated that activity of glutathione peroxidase 4 (GPX4) and catalytic subunit solute carrier family 7 member 11 (SLC7A11) decreased significantly, and protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and 15 Lipoxygenase 1 (15-LO1) upregulated prominently compared with mice in normal control group. Conclusions: These in all indicated that the AHR, airway inflammation, lipid peroxidation and ROS level increased in HDM-induced asthma, and HDM inhalation caused ferroptosis in the lungs, which helped to form a better understanding of the pathogenesis of allergic asthma and targeted treatment strategies.

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“…In line with this, ferroptosis inducers are thought to represent a potential treatment strategy for therapy-resistant cancers [13]. Previous studies have shown that some genes such as SLC7A11 and ACADSB can attenuate the proliferation of CC cells via triggering ferroptosis [14,15]. In addition, some drugs have been shown to suppress CC by stimulating some level of ferroptosis [16].…”

Section: Introductionmentioning

confidence: 94%

Identification of a ferroptosis-related gene signature predictive model in colon cancer

et al. 2021

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Background The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. Methods The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. Results Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. Conclusion A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

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Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis

Cited by 113 publications

References 35 publications

Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer

Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer

Environmental Allergens House Dust Mites-induced Asthma Causes Ferroptosis in the Lungs

Identification of a ferroptosis-related gene signature predictive model in colon cancer

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