ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Lü, Di; Yang, Zhiyu; Qing, Xiao; Gao, Shanjun; Sun, Suofeng; Luo, Xiaoying; Li, Zhen; Zhang, Xiulei; Li, Xiuling

doi:10.1002/cbin.11443

Cited by 46 publications

(35 citation statements)

References 39 publications

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“…e potential mechanisms analysis also supported that more tumor metastasis-associated pathways were activated in high-score samples. Previous studies also proved that ferroptosis can affect tumor migration and invasion including colorectal cancer [45], melanoma [46], breast cancer [47], prostate tumor [48], and so on. Collectively, this work proposed that the activation of ferroptosis may affect ovarian cancer progression by modulating tumor metastasis.…”

Section: Discussionmentioning

confidence: 89%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

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Section: Discussionmentioning

confidence: 89%

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Yang

Huang

et al. 2021

Journal of Oncology

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“…Cell transfection was performed by ENO3 and GPX4 lentiviral transfection harboring with overexpressed (OE) or short hairpin RNA (shRNA) plasmid of ENO3 and GPX4 as previously described (26). Briefly, L02 cells at a density of 3×10 5 cells/well were seeded in a six-well plate prior to transfection.…”

Section: Cell Transfectionmentioning

confidence: 99%

ENO3 promoted the progression of NASH by negatively regulating ferroptosis via elevation of GPX4 expression and lipid accumulation

Lü¹,

Qing²,

Yang³

et al. 2021

Ann Transl Med

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Background: ENO3 expression is upregulated in Non-alcoholic fatty liver disease (NAFLD) patient tissues, demonstrated that ENO3 might play crucial roles in NAFLD. However, the mechanism of ENO3 in NAFLD remains unclear. Therefore, this study aimed to investigate the regulatory mechanism of ENO3 in the progression of non-alcoholic steatohepatitis (NASH) in vivo and vitro NASH model. Methods: In vivo and vitro NASH model were established by methionine-choline deficient (MCD)-diet feeding and high free fatty acid (HFFA) induction in L02 cells. Loss and gain function of ENO3 and GPX4 was performed to study the mechanism in NASH. Western blot was used to detect the expression of ENO3 and GPX4. Hematoxylin and eosin (H&E), picrosirius Red and Oil Red O staining was used to evaluate histopathology of liver in NASH model. Ferroptosis indicators were measured by assay kits according to the manufacturer's instructions.Results: NASH mouse model was successfully established induced by MCD diet with steatosis, inflammatory infiltration, ballooning and fibrosis observed in the liver tissue. The expression of ENO3 and GPX4 was significantly elevated while ferroptosis was inhibited in NASH mice and cell model. Upregulation of both ENO3 and GPX4 could promote the lipid accumulation in L02 cells. In addition, overexpressed ENO3 attenuated the status of ferroptosis.Conclusions: In the present study, we demonstrate that ENO3 promoted the progression of NASH by negatively regulating ferroptosis via elevating GPX4 expression and lipid accumulation. These findings provided solid foundation for the mechanism of ferroptosis on the progression of NASH regulated by ENO3, suggesting that ENO3 may be a potential therapeutic target for NASH.

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“…It has been proved that resistance to ferroptosis reduced the efficacy of sorafenib and was associated with poor prognosis in hepatocellular carcinoma ( Houessinon et al, 2016 ; Liang et al, 2020 ). Lu et al reported that ferroptosis was suppressed in colorectal cancer, leading to short overall survival of colorectal cancer patients ( Lu et al, 2020 ). Similarly, ferroptosis plays an important role in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer

Zhang

Ping

et al. 2021

Front. Mol. Biosci.

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Background: Ferroptosis, a regulated cell death which is driven by the iron-dependent peroxidation of lipids, plays an important role in cancer. However, studies about ferroptosis-related Long non-coding RNAs (lncRNAs) in breast cancer (BC) are limited. Besides, the prognostic role of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer remain unclear. This study aimed to explore the potential prognostic value of ferroptosis-related lncRNAs and their relationship to immune microenvironment in breast cancer.Methods: RNA-sequencing data of female breast cancer patients were downloaded from TCGA database. 937 patients were randomly separated into training or validation cohort in 2:1 ratio. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 239 reported ferroptosis-related genes. A ferroptosis-related lncRNAs signature was constructed with univariate and multivariate Cox regression analyses in the training cohort, and its prognostic value was further tested in the validation cohort.Results: An 8-ferroptosis-related-lncRNAs signature was developed by multivariate Cox regression analysis to divide patients into two risk groups. Patients in the high-risk group had worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed the risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The area under time-dependent ROC curve (AUC) reached 0.853 at 1 year, 0.802 at 2 years, 0.740 at 5 years in the training cohort and 0.791 at 1 year, 0.778 at 2 years, 0.722 at 5 years in the validation cohort. Further analysis demonstrated that immune-related pathways were significantly enriched in the high-risk group. Analysis of the immune cell infiltration landscape showed that breast cancer in the high-risk group tended be immunologically “cold”.Conclusion: We identified a novel ferroptosis-related lncRNA signature which could precisely predict the prognosis of breast cancer patients. Ferroptosis-related lncRNAs may have a potential role in the process of anti-tumor immunity and serve as therapeutic targets for breast cancer.

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ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

Cited by 46 publications

References 39 publications

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

Ferroptosis-Related Gene Signature Promotes Ovarian Cancer by Influencing Immune Infiltration and Invasion

ENO3 promoted the progression of NASH by negatively regulating ferroptosis via elevation of GPX4 expression and lipid accumulation

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer

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