FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells

Zeng, Ye; Zhuo, Qifeng; Hu, Qiangsheng; Xu, Xiaowu; liu, Mengqi; Zhang, Zheng; Xu, Wenyan; Liu, Wensheng; Fan, Guixiong; Qin, Yi; Yu, Xianjun; Ji, Shunrong

doi:10.1016/j.redox.2020.101807

Cited by 170 publications

(128 citation statements)

References 42 publications

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“…Mutation of PI3K-AKT-mTOR signaling protects cancer cells from ferroptosis death through SREBP1/SCD1-mediated lipogenesis [33]. Besides, various studies have reported that ferroptosis can mitigate gemcitabine resistance and lead to a favorable prognosis in pancreatic cancer cells [34,35], which is consistent with the result of our study: most of the Fe-LPM are protective factors based on the univariate Cox regression analysis.…”

Section: Discussionsupporting

confidence: 91%

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Chen¹,

Gao²,

Zang³

et al. 2021

Preprint

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Background: Pancreatic cancer (PC) is one of the most lethal malignancies, the mortality and morbidity of which have been increasing over the past decade. Ferroptosis, a newly identified iron-dependent pattern of cell death, can be induced by iron chelators and small lipophilic antioxidants. Nonetheless, the prognostic significance of ferroptosis-related lncRNAs in PC remains to be explicated. Methods: We obtained the lncRNA expression matrix and clinicopathological information of PC patients from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) datasets in the current study. Pearson correlation analysis was conducted to delve into the ferroptosis-related lncRNAs, and univariate Cox analysis was implemented to examine the prognostic values in PC patients. The least absolute shrinkage and selection operator Cox (LASSO-Cox) analysis was performed to establish a ferroptosis-related lncRNA prognostic marker (Fe-LPM). Furthermore, we adopted a multivariate Cox regression to establish a nomogram. Gene set enrichment analysis (GSEA) and a competing endogenous RNA (ceRNA) network were also created.Results: The eight Fe-LPM (including SLC16A1-AS1, SETBP1-DT, ZNF93-AS1, SLC25A5-AS1, AC073896.2, LINC00242, PXN-AS1 and AC036176) was confirmed, and displayed a sturdy prognostic capability in the training and validation dataset. We established a nomogram based on risk score, age, pathological T stage and primary therapy outcome. GSEA revealed that several ferroptosis-related pathways are enriched in low-risk subgroups. A ceRNA network (including 4 lncRNAs, 27 miRNAs and 57 mRNAs) was also constructed to provide us some clues for finding the potential functions of these ferroptosis-related lncRNAs in PC.Conclusion: The eight Fe-LPM can be utilized for anticipating the overall survival (OS) of PC patients, which are meaningful to guiding clinical strategies of PC.

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Section: Discussionsupporting

confidence: 91%

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Chen¹,

Gao²,

Zang³

et al. 2021

Preprint

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“…They observed that inhibition of SCD significantly potentiated the antitumor effect of ferroptosis inducers. Ye et al ( 30 ) reported that SCD inhibited both ferroptosis and apoptosis in pancreatic cancer cells. In our study, we verified the aberrant expression of SCD in BLCA tissues and found that samples with high T stage or MIBC expressed higher SCD, which assumed that SCD may play an important oncogenic role in BLCA.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Ferroptosis-Related Gene Prognostic Signature in Bladder Cancer

et al. 2021

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BackgroundFerroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRG) in bladder cancer (BLCA) have not been well examined.MethodsFRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs were investigated by functional enrichment analyses. The prognostic FRG signature was identified by univariate cox regression and least absolute shrinkage and selection operator (LASSO) analysis, which was validated in TCGA cohort and Gene Expression Omnibus (GEO) cohort. Subsequently, the nomogram integrating risk scores and clinical parameters were established and evaluated. Additionally, Gene Set Enrichment Analyses (GSEA) was performed to explore the potential molecular mechanisms underlying our prognostic FRG signature. Finally, the expression of three key FRGs was verified in clinical specimens.ResultsThirty-two significantly different FRGs were identified from TCGA–BLCA cohort. Enrichment analyses showed that these genes were mainly related to the ferroptosis. Seven genes (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, and PRDX6) were then identified to develop a prognostic signature. The Kaplan–Meier analysis confirmed the predictive value of the signature for overall survival (OS) in both TCGA and GEO cohort. A nomogram integrating age and risk scores was established and demonstrated high predictive accuracy, which was validated through calibration curves and receiver operating characteristic (ROC) curve [area under the curve (AUC) = 0.690]. GSEA showed that molecular alteration in the high- or low-risk group was closely associated with ferroptosis. Finally, experimental results confirmed the expression of SCD, SRC, and PRDX6 in BLCA.ConclusionHerein, we identified a novel FRG prognostic signature that maybe involved in BLCA. It showed high values in predicting OS, and targeting these FRGs may be an alternative for BLCA treatment. Further experimental studies are warranted to uncover the mechanisms that these FRGs mediate BLCA progression.

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“…Hence, finding new strategies for comprehensive treatment of pancreatic cancer is urgent. 71 , 72 MA can inhibit human pancreatic cancer Panc‐28 cells with an IC 50 value of 49.2 ± 0.5 μM. MA also significantly induced autophagy at a concentration of 50 μM.…”

Section: Anticancer Properties Of Maslinic Acidmentioning

confidence: 94%

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

Yu¹,

Xie²,

Cao³

et al. 2021

DDDT

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Cancer is still an insurmountable problem for humans and critically attacking human health. In recent years, natural products have gained increasing attention in the field of anti-tumor due to their extensive sources and minimal side effects. Maslinic acid (MA), a pentacyclic triterpene acid mainly derived from the olive tree (Olea europaea L.) has been confirmed to possess great anti-cancer effects. This paper reviewed the inhibitory effect of MA and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others. MA inhibited the proliferation of various tumor cells and showed lower IC 50 values in melanoma 518A2 cells and gastric cancer MKN28 cells compared with other cell lines. A series of semi-synthetic derivatives obtained by modifying MA chemical structure have been shown to have high cytotoxicity to human tumor cell lines, but low cytotoxicity to nonmalignant cells, which is conducive to developing its potential as a chemotherapeutic agent. These studies suggest that MA derivatives have broad prospects in the development of antitumor therapeutics in the future and warrant further study.

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FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells

Cited by 170 publications

References 42 publications

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Identification of a Novel Ferroptosis-Related Gene Prognostic Signature in Bladder Cancer

The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review

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