IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells

Xu, Xin; Cui, Jiangtao; Wang, Hong; Ma, Lifang; Zhang, Xiao; Guo, Weijie; Xue, Xiangfei; Wang, Yikun; Qiu, Shi; Tian, Xiaoting; Miao, Yayou; Wu, Mengyi; Yu, Yongchun; Xu, Yunhua; Wang, Jiayi; Qiao, Yongxia

doi:10.1016/j.mtbio.2022.100503

Cited by 35 publications

(19 citation statements)

References 74 publications

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“…Meanwhile, ACSL3 inhibited lipid peroxidation and then repressed ferroptosis by promoting the secretion of oleic acid from adipocytes 39 . Via elevating the expression of ACSL3, methionine adenosyltransferase 2A (MAT2A) 40 , insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) 41 and baicalein 42 were able to repress ferroptosis. Consistent with these results, our results showed that elevated expression of ACSL3 by MIR100HG repressed ferroptosis in lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

Liu

Wang

Chen

et al. 2023

Preprint

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MIR100HG, a lncRNA residing on chromosome 11, affected the occurrence and prognosis of many cancers. Although previous reports revealed that MIR100HG was down-regulated in lung tumor tissues and prolonged the survival time of lung cancer patients, its detailed mechanism remained elusive. In our study, the mechanism of MIR100HG on ferroptosis in lung cancer cells was investigated. RT-PCR revealed that MIR100HG was upregulated by RSL3. Subsequently, MIR100HG was found to affect intracellular GSH and ROS levels and promote RSL3-induced ferroptosis in lung cancer cells. In vitro experiments, including transcriptomics sequencing, RT-PCR, western blot and RNA immunoprecipitation (RIP), found that MIR100HG was mainly located in the nucleus and negatively regulated the expression of ACSL3 via affecting the association of HuR and the mRNA of ACSL3. Analyzing RNA-sequencing data in TCGA database and measuring their expression levels unveiled that MIR100HG and ACSL3 were differentially expressed between lung cancer and paired-paracancerous tissues. Moreover, KM plotter results indicated that MIR100HG and ACSL3 affected the prognosis of lung cancer patients. Although still needing to be further investigated, our results showed that the MIR100HG-ACSL3 axis regulated ferroptosis in lung cancer cells and affected the occurrence and prognosis of lung cancer for the first time.

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Section: Discussionmentioning

confidence: 99%

MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

Liu

Wang

Chen

et al. 2023

Preprint

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“…CCL20 is associated with certain programmed cell deaths, such as autophagy, iron apoptosis, and pyroptosis (54). ACSL3 activates exogenous monounsaturated fatty acids and promotes oleic acid secretion in fat cells, thereby inhibiting lipid peroxidation and iron apoptosis (55). EREG, one of the epidermal growth factor receptor (EGFR) ligands, is typically lowly expressed in most normal tissues.…”

Section: Discussionmentioning

confidence: 99%

Classical Monocyte Marker Gene Signatures (CMMGS) Identified by Analysis of Single-Cell and Bulk-RNA Sequencing to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma

LIN,

Huang,

Ren

et al. 2023

Preprint

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Background Classical monocytes, pivotal in the innate immune response, wield considerable influence over cancer prognosis and response to immunotherapy. Our aim was to construct lung adenocarcinoma (LUAD) prognostic signature associated with Classical monocytes.Methods This study encompassed 1,822 samples drawn from diverse public datasets. Initially, we conducted an comprehensive analysis of lung adenocarcinoma (LUAD) single-cell RNA sequencing data obtained from the Gene Expression Omnibus (GEO), identifying 145 marker genes specific to classical monocyte. Univariate Cox regression and Least Absolute Shrinkage Operator (LASSO) analyses were performed on the TCGA training cohort to construct a signature for classical monocyte marker genes.Result Patients in the TCGA LUAD cohort were categorized into high- and low-risk groups based on polygenic prognostic signature derived from these marker genes. The predictive capacity of this signature was robustly validated across distinct clinical subgroups and GEO cohorts. Notably, this signature emerged as an independent prognostic indicator via multivariate analysis. Low-risk patients exhibited heightened immune cell infiltration, correlating inversely with inflammatory activity and risk score. Conversely, the low-risk group demonstrated amplified abundance and diversity in T-cell receptor (TCR) repertoires, higher Immunophenotype scores (IPS), and lower Tumor Immune Dysfunction and Exclusion (TIDE) scores. Significantly, an assessment across three GEO immunotherapy cohorts showcased superior immunotherapeutic response and prognosis among low-risk patients compared to their high-risk counterparts.Conclusion In summary, our study introduces a novel signature rooted in monocyte marker genes that proficiently prognosticates and predicts immunotherapeutic response in LUAD patients.Supplementary Information: Supplementary information is uploaded in the attached document.

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“…The post transcriptional regulation of ULK1 was altered by FTO, which led to the increased expression of ULK1 and induction of autophagy [ 145 ]. IGF2BP3 inhibited ferroptosis by binding to m6A methylated mRNA encoding anti-ferroptotic factors, including glutathione peroxidase 4 (GPX4), solute carrier family 3 member 2 (SLC3A2), and ferritin heavy chain H1 (FTH1), in lung adenocarcinoma cells [ 146 ]. Thus, it will be interesting to examine the relationship between autophagy and ferroptosis.…”

Section: The Regulatory Role Of M6a Modifications In Autophagymentioning

confidence: 99%

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

Shim

Jeoung

2023

IJMS

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RNA methylations play critical roles in RNA processes, including RNA splicing, nuclear export, nonsense-mediated RNA decay, and translation. Regulators of RNA methylations have been shown to be differentially expressed between tumor tissues/cancer cells and adjacent tissues/normal cells. N6-methyladenosine (m6A) is the most prevalent internal modification of RNAs in eukaryotes. m6A regulators include m6A writers, m6A demethylases, and m6A binding proteins. Since m6A regulators play important roles in regulating the expression of oncogenes and tumor suppressor genes, targeting m6A regulators can be a strategy for developing anticancer drugs. Anticancer drugs targeting m6A regulators are in clinical trials. m6A regulator-targeting drugs could enhance the anticancer effects of current chemotherapy drugs. This review summarizes the roles of m6A regulators in cancer initiation and progression, autophagy, and anticancer drug resistance. The review also discusses the relationship between autophagy and anticancer drug resistance, the effect of high levels of m6A on autophagy and the potential values of m6A regulators as diagnostic markers and anticancer therapeutic targets.

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IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells

Cited by 35 publications

References 74 publications

MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

Classical Monocyte Marker Gene Signatures (CMMGS) Identified by Analysis of Single-Cell and Bulk-RNA Sequencing to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma

Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance

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