RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways

Qu, Jianwei; Hou, Yifan; Chen, Qingxiao; Chen, Jing; Li, Yang; Zhang, Enfan; Gu, Huiyao; Xu, Rui‐hua; Liu, Yang; Cao, Wen; Zhang, Jinna; Cao, Liqin; He, Jingsong; Zhang, Cai

doi:10.1038/s41388-021-02095-8

Cited by 28 publications

(16 citation statements)

References 69 publications

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“…In addition, our study also found an interaction between ELAVL1 and m6A regulators in almost all tumors. Cumulative studies have confirmed that m6A imbalance is closely related to tumors ( 13 – 16 ). Therefore, we believe that although high expression of ELAVL1 is not the cause of tumorigenesis, it may be one of the key molecules in this process.…”

Section: Discussionmentioning

confidence: 95%

“…Several studies have shown that m6A dysregulation is associated with tumorigenesis and cancer progression ( 13 – 16 ). The expression of multiple m6A regulators, including METTL3, FTO, ALKBH5, and YTHDF3, is significantly changed in different tumors, including lung cancer, osteosarcoma, gastric cancer, melanoma, and cholangiocarcinoma ( 17 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

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ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

Cai

Bai

et al. 2022

Front. Oncol.

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N6-Methyladenosine (m6A) imbalance is an important factor in the occurrence and development of prostate cancer (PCa). Many m6A regulators have been found to be significantly dysregulated in PCa. ELAVL1 is an m6A binding protein that can promote the occurrence and development of tumors in an m6A-dependent manner. In this study, we found that most m6A regulators were significantly dysregulated in PCa, and some m6A regulators were associated with the progression-free interval. Mutations and copy number variations of these m6A regulators can alter their expression. However, ELAVL1 mutations were not found in PCa. Nevertheless, ELAVL1 upregulation was closely related to PCa proliferation. High ELAVL1 expression was also related to RNA metabolism. Further experiments showed that ELAVL1 interacted with other m6A regulators and that several m6A regulatory mRNAs have m6A sites that can be recognized by ELAVL1. Additionally, protein–protein interactions occur between ELAVL1 and other m6A regulators. Finally, we found that the dysregulation of ELAVL1 expression occurred in almost all tumors, and interactions between ELAVL1 and other m6A regulators also existed in almost all tumors. In summary, ELAVL1 is an important molecule in the development of PCa, and its interactions with other m6A regulators may play important roles in PCa progression.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

Cai

Bai

et al. 2022

Front. Oncol.

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“…It is apparent that m 6 A and its related factors (e.g., FTO) are involved in the progression of MM and provide a potential therapeutic target. Furthermore, ALKBH5 is similarly confirmed to be overexpressed in MM and predicts a worse prognosis for MM patients [ 136 ]. Functionally, the downregulation of ALKBH5 promotes tumor cell death and suppresses the growth of MM cells in vitro, exerting a tumorigenic effect.…”

Section: M 6 a Methylation Modifications And Hematological Malignanciesmentioning

confidence: 99%

The Role of N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies

Zhao

Peng

2022

Cancers

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Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents. Therefore, this review elaborates on the biological characteristics and normal hematopoietic regulatory functions of m6A methylation modifications and their role in the pathogenesis of hematologic malignancies.

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“…The FTO and ALKBH5 both belong to the AlkB family. However, the function of m6A modification erasure is independent (He et al, 2021; Qu et al, 2022). FTO and ALKBH5 localize in the nucleus with low expression in the cytoplasm.…”

Section: Composition and Function Of M6a‐related Proteinsmentioning

confidence: 99%

N6‐methyladenosine (m6A) modification in gynecological malignancies

Zhang

Liu

2022

Journal Cellular Physiology

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N6-methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. m6A modified RNA is specifically recognized and bound by m6A recognition proteins, which mediate splicing, maturation, exonucleation, degradation, and translation. In gynecologic malignancies, m6A RNA modification-related molecules are expressed aberrantly, significantly altering the posttranscriptional methylation level of the target genes and their stability. The m6A modification also regulates related metabolic pathways, thereby controlling tumor development. This review analyzes the composition and mode of action of m6A modification-related proteins and their biological functions in the malignant progression of gynecologic malignancies, which provide new ideas for the early clinical diagnosis and targeted therapy of gynecologic malignancies.

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RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways

Cited by 28 publications

References 69 publications

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

ELAVL1 promotes prostate cancer progression by interacting with other m6A regulators

The Role of N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies

N6‐methyladenosine (m6A) modification in gynecological malignancies

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