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 20 publications

(2 citation statements)

References 74 publications

(90 reference statements)

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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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“…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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Hypomethylation‐associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation‐mediated degradation of SND1

Lai,

Wan,

Zhang

et al. 2024

Molecular Carcinogenesis

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DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real‐time polymerase chain reaction (RT‐qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull‐down assays. The functional significance of LINC00987 and SND1 in Calu‐3 and NCI‐H1688 cells was evaluated in vitro through CCK‐8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5‐Aza‐CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

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

Cited by 20 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

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

Hypomethylation‐associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation‐mediated degradation of SND1

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