Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer

Moody, M. Anthony; Kong, Pengfei; Huang, Yakai; Wang, Jiangli; Liu, Xiaocen; Hu, Yiren; Chen, Xingxing; Du, Chunyan; Yang, Hui

doi:10.1016/j.freeradbiomed.2022.02.015

Cited by 36 publications

(27 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Liu

Wang

Chen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…A study has shown that ACSL3 was upregulated by MAT2A, which mediated the formation of S-adenosylmethionine (SAM), the main biological methyl donor. Mechanistically, MAT2A increases the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter region and subsequently causes ferroptosis resistance [ 43 ].…”

Section: Acsl3 and Acsl4 In Cancersmentioning

confidence: 99%

ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

Yang

Zhu

Wang

et al. 2022

Cancers

View full text Add to dashboard Cite

The long-chain fatty acyl CoA synthetase (ACSLs) family of enzymes contributes significantly to lipid metabolism and produces acyl-coenzyme A by catalyzing fatty acid oxidation. The dysregulation of ACSL3 and ACSL4, which belong to the five isoforms of ACSLs, plays a key role in cancer initiation, development, metastasis, and tumor immunity and may provide several possible therapeutic strategies. Moreover, ACSL3 and ACSL4 are crucial for ferroptosis, a non-apoptotic cell death triggered by the accumulation of membrane lipid peroxides due to iron overload. Here, we present a summary of the current knowledge on ACSL3 and ACSL4 and their functions in various cancers. Research on the molecular mechanisms involved in the regulation of ferroptosis is critical to developing targeted therapies for cancer.

show abstract

“…Ferroptosis is a newly discovered form of regulated cell death, which involves the accumulation of iron-dependent lipid peroxides and leads to fatal cell damage ( Zhang et al, 2020 ). Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming iron-dependent lipid peroxides, is considered an emerging cancer suppression mechanism for gastric cancer (GC) ( Ma et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Although great progress has been made in the diagnosis and treatment of GC in recent years, there is still lack of effective diagnostic markers, and the prognosis of advanced GC is not optimistic. Studies have started to reveal the essential role of ferroptosis in GC ( Lee et al, 2020 ; Zhang et al, 2020 ; Guan et al, 2022 ; Ma et al, 2022 ). Ferroptosis plays an important regulatory role in the occurrence, development, invasion, migration, diagnosis, drug resistance, and prognosis of GC ( Gomaa et al, 2019 ; Zhang et al, 2020 ; Liu Y. et al, 2021 ; Guan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer

Lü

Chen

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Gastric cancer (GC) is a malignant cancer of the digestive tract and is a life-threatening disease worldwide. Ferroptosis is a newly discovered form of regulated cell death, which involves the accumulation of iron-dependent lipid peroxides. It has been found that ferroptosis plays an important regulatory role in the occurrence, development, drug resistance, and prognosis of GC. Non-coding RNAs (ncRNAs) play a critical role in the occurrence and progression of a variety of diseases including GC. In recent years, the role of ferroptosis and ferroptosis-related ncRNAs (miRNA, lncRNA, and circRNA) in the occurrence, development, drug resistance, and prognosis of GC has attracted more and more attention. Herein, we briefly summarize the roles and functions of ferroptosis and ferroptosis-related ncRNAs in GC tumorigenesis, development, and prognosis. We also prospected the future research direction and challenges of ferroptosis and ferroptosis-related ncRNAs in GC.

show abstract

Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer

Cited by 36 publications

References 40 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

ACSL3 and ACSL4, Distinct Roles in Ferroptosis and Cancers

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer

Contact Info

Product

Resources

About