IGF2BP3-NRF2 axis regulates ferroptosis in hepatocellular carcinoma

Lu, Zhihua; Yang, Hao; Shao, Yuting; Sun, Weiji; Jiang, Yuanhui; Li, Jie

doi:10.1016/j.bbrc.2022.08.040

Cited by 31 publications

(12 citation statements)

References 29 publications

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“…IGF2BP3 can stabilize NRF2 mRNA by binding to the m6A site of NRF2 mRNA. The final conclusion was that the IGF2BP3-NRF2 axis could be used as an important mechanism for regulating ferroptosis during SF treatment in HCC 16 . CircARID1A acted as a scaffold to promote the interplay of IGF2BP3 and SLC7A5 mRNA, which ultimately increased the stability of SLC7A5 mRNA and thus promoted gastric cancer cell proliferation 38 .…”

Section: Resultsmentioning

confidence: 99%

“…IGF2BP3, as a protein coding gene, encodes proteins that contain several KH domains, which are important in RNA binding, RNA synthesis and metabolism 14 . Although IGF2BP3 has been discovered to exert cancer-promoting functions in HCC 15 , 16 , comprehensive bioinformatics analysis of IGF2BP3 in HCC and pan-cancer is scarce. The purpose of this study is to provide more new ideas on the pathogenic mechanisms and more therapeutic possibilities for the treatment of HCC and pan-cancer.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer

Qin,

Jin,

et al. 2024

J. Cancer

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Insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a critical m6A reader. It encodes proteins that contain several KH domains, which are important in RNA binding, RNA synthesis and metabolism. Lots of researches have studied the malignant potential of m6A readers in tumors. However, the biological functional analysis of IGF2BP3 in hepatocellular carcinoma (HCC) and pan-cancer is not comprehensive. In this study, we used a bioinformatics approach to comprehensively analyze the significance of IGF2BP3 in HCC through analyzing its expression, mutation, prognosis, protein-protein interaction (PPI) network, functional enrichment, and the correlation with ferroptosis, stemness as well as immune modulation in HCC. IGF2BP3 presented a negative correlation with the ferroptosis molecule NFE2L2, and a positive correlation with the ferroptosis molecule SLC1A5 as well as the immune checkpoint HAVCR2. In addition, we also analyzed IGF2BP3 expression, prognosis and immune modulation in pan-cancer, revealing the prognostic value of IGF2BP3 in a variety of tumors. Finally, we verified the biological functions of IGF2BP3 in HCC through various experiments. The data showed that IGF2BP3 may enhance the proliferation, colony formation and invasion capacities of HCC cells, and IGF2BP3 is mainly positively correlated with the expression level of stemness marker SOX2. In conclusion, IGF2BP3 had a potential to be a new perspective biomarker in forecasting the immune response, ferroptosis, stemness and prognosis of HCC or even pan-cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer

Qin,

Jin,

et al. 2024

J. Cancer

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“…These findings suggest that IGF2BP3 likely exerts a regulatory function over GPX4 in a post-transcriptional manner. Previous study has indicated that IGF2BP3 has the capability to bind to NRF2 mRNA, thereby influencing its mRNA stability [ 39 ]. Additionally, GPX4 has been identified as a downstream target of NRF2 [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

Depletion of the N6-Methyladenosine (m6A) reader protein IGF2BP3 induces ferroptosis in glioma by modulating the expression of GPX4

Deng,

Di,

Chen

et al. 2024

Cell Death Dis

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Emerging evidence highlights the multifaceted contributions of m6A modifications to glioma. IGF2BP3, a m6A modification reader protein, plays a crucial role in post-transcriptional gene regulation. Though several studies have identified IGF2BP3 as a poor prognostic marker in glioma, the underlying mechanism remains unclear. In this study, we demonstrated that IGF2BP3 knockdown is detrimental to cell growth and survival in glioma cells. Notably, we discovered that IGF2BP3 regulated ferroptosis by modulating the protein expression level of GPX4 through direct binding to a specific motif on GPX4 mRNA. Strikingly, the m6A modification at this motif was found to be critical for GPX4 mRNA stability and translation. Furthermore, IGF2BP3 knockdown glioma cells were incapable of forming tumors in a mouse xenograft model and were more susceptible to phagocytosis by microglia. Our findings shed light on an unrecognized regulatory function of IGF2BP3 in ferroptosis. The identification of a critical m6A site within the GPX4 transcript elucidates the significance of post-transcriptional control in ferroptosis.

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“…Besides, Gao et al (2020) suggested IGF2BP3 can enhance miR191-5p-mediated inhibition of ZO-1 signaling, thus acting as a driver of malignancy of HCC. Furthermore, loss of IGF2BP3 obviously induces ferroptosis in HCC cells by decreasing NRF2 mRNA stability in an m 6 A-dependent manner after sorafenib treatment ( Lu et al, 2022 ). Conversely, another study showed that IGFBP-3 suppresses HCC cell proliferation via inhibition of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) expression ( Ma et al, 2016 ).…”

Section: The Implications Of M 6 a Regulators In H...mentioning

confidence: 99%

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications

Zhao,

Li,

et al. 2024

Front. Pharmacol.

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Liver cancer remains as the third leading cause of cancer-related death globally as of 2020. Despite the significant progress made in the field of liver cancer treatment, there is still a lack of effective therapies in patients with advanced cancer and the molecular mechanisms underlying liver cancer progression remain largely elusive. N6-methyladenosine (m6A) modification, as the most prevalent and abundant internal RNA modification in eukaryotic RNAs, plays an essential role in regulating RNA metabolism including RNA splicing, stability, translation, degradation. To date, there is mounting evidence showing that m6A dysregulation is closely associated with the onset and development of many tumors including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatoblastoma (HB). In this review, we summarize the last research progress regarding the functions of m6A-related regulators in liver cancer and its underlying mechanisms. Additionally, we also discuss the therapeutic applications of m6A-based inhibitors in liver cancer treatment.

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IGF2BP3-NRF2 axis regulates ferroptosis in hepatocellular carcinoma

Cited by 31 publications

References 29 publications

Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer

Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer

Depletion of the N6-Methyladenosine (m6A) reader protein IGF2BP3 induces ferroptosis in glioma by modulating the expression of GPX4

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications

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