METTL3‐mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis

Wang, An; Chen, Xiaofeng; Li, Dongen; Yang, Lifen; Jianshuai, Jiang

doi:10.1002/jcla.23931

Cited by 17 publications

(8 citation statements)

References 28 publications

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“…For example, METTL3 synergizes with hepatitis B X-interacting protein (HBXIP) to regulate the abundance of m6A modification of hypoxia-inducible factor-1 alpha (HIF-1α), resulting in metabolic reprogramming and malignant progression of hepatocellular carcinoma cells [ 10 ]. METTL3 could also drive hepatocellular carcinoma progression by mediating m6A modification of ubiquitin-specific processing protease 7 (USP7) [ 11 ] or abnormal spindle-like microcephaly (ASPM) [ 12 ]. However, the role of METTL3 in CCA progression remains obscure.…”

Section: Introductionmentioning

confidence: 99%

METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10

et al. 2022

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Objective N6-methyladenosine (m6A) RNA methylation is involved in governing the mechanism of tumor progression. We aimed to excavate the biological role and mechanism of the m6A methyltransferase METTL3 in cholangiocarcinoma (CCA). Methods METTL3 expression was determined by database and tissue microarray analyses. The role of METTL3 in CCA was explored by loss- and gain-of-function experiments. The m6A target of METTL3 was detected by RNA sequencing. The role of AKR1B10 in CCA was explored, and the association between METTL3 and AKR1B10 was confirmed by rescue experiments. Result METTL3 expression was upregulated in CCA tissue, and higher METTL3 expression was implicated in poor prognoses in CCA patients. Overexpression of METTL3 facilitated proliferation, migration, invasion, glucose uptake, and lactate production in CCA cells, whereas knockdown of METTL3 had the opposite effects. We further found that METTL3 deficiency inhibited CCA tumor growth in vivo. RNA sequencing and MeRIP-qPCR confirmed that METTL3 enhanced AKR1B10 expression and m6A modification levels. Furthermore, METTL3 directly binds with AKR1B10 at an m6A modification site. A CCA tissue microarray showed that AKR1B10 expression was upregulated in CCA tissue and that silencing AKR1B10 suppressed the malignant phenotype mentioned above in CCA. Notably, knockdown of AKR1B10 rescued the tumor-promoting effects induced by METTL3 overexpression. Conclusion Elevated METTL3 expression promotes tumor growth and glycolysis in CCA through m6A modification of AKR1B10, indicating that METTL3 is a potential target for blocking glycolysis for application in CCA therapy.

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Section: Introductionmentioning

confidence: 99%

METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10

et al. 2022

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“…Previous studies showed that ASPM was highly expressed in hepatocellular carcinoma (HCC), and the high expression of ASPM was correlated with poor HCC prognosis. Mechanism studies showed that METTL3 promoted HCC cells growth and metastasis via m 6 A modification of ASPM ( Wang et al, 2021 ). Mettl14-mediated m 6 A played a critical role in liver regeneration by regulating the expression of polypeptide-processing proteins and maintaining endoplasmic reticulum homeostasis ( Cao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Differentially Expressed Profiles of mRNA N6-Methyladenosine in Colorectal Cancer

Li¹,

Guo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Aim: To comprehensively profile the landscape of the mRNA N6-methyladenosine (m6A) modification in human colorectal cancer (CRC).Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was explored to compare the difference in mRNA N6-methyladenosine (m6A) methylation between CRC tissues and adjacent normal control (NC) tissue. RNA-sequencing (RNA-seq) was performed to transcribe differentially expressed mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq data was conducted to predict RNA-binding proteins (RBPs).Results: MeRIP-seq identified 1110 differentially m6A methylated sites (DMMSs) and 980 differentially m6A methylated genes (DMMGs) in CRC, with 50.13% of all modified genes showing unique m6A-modified peaks in CRC. RNA-seq showed 915 upregulated genes and 1463 downregulated genes in CRC. QRT-PCR verified the RNA-seq results by detecting the expression of some mRNAs. Conjoint analysis of MeRIP-seq and RNA-seq identified 400 differentially m6A methylated and expressed genes (DEGs), and pathway analysis detected that DMMGs and DEGs were closely related to cancer. After analyzing these DMMGs and DEGs through the GEPIA database, we found that the expression of B3GNT6, DKC1, SRPK1, and RIMKLB were associated with prognosis, and the expression of B3GNT6 and RIMKLB were associated with clinical stage. 17 RBPs were identified based on the DMMGs and DEGs, among which FXR1, FXR2, FMR1, IGF2BP2, IGF2BP3, and SRSF1 were obviously highly expressed in CRC, and FMR1, IGF2BP2, and IGF2BP3 were closely related to methylation, and might be involved in the development of CRC.Conclusion: This study comprehensively profiled m6A modification of mRNAs in CRC, which revealed possible mechanisms of m6A-mediated gene expression regulation.

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“…Many studies on m6A regulators in liver cancer have been performed, and the main role of m6A has been shown to be cancer promotion. METTL3 regulates the expression of the downstream targets ASPM [ 222 ] and SOCS2 [ 40 ] in a m6A-dependent manner and promotes the proliferation and metastasis of liver cancer. KIAA1429 regulates circular RNA DLC1 to promote cancer through m6A mediation [ 223 ].…”

Section: M6a and Cancersmentioning

confidence: 99%

Role of m6A writers, erasers and readers in cancer

et al. 2022

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The N(6)-methyladenosine (m6A) modification is the most pervasive modification of human RNAs. In recent years, an increasing number of studies have suggested that m6A likely plays important roles in cancers. Many studies have demonstrated that m6A is involved in the biological functions of cancer cells, such as proliferation, invasion, metastasis, and drug resistance. In addition, m6A is closely related to the prognosis of cancer patients. In this review, we highlight recent advances in understanding the function of m6A in various cancers. We emphasize the importance of m6A to cancer progression and look forward to describe future research directions.

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METTL3‐mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis

Cited by 17 publications

References 28 publications

METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10

METTL3 promotes glycolysis and cholangiocarcinoma progression by mediating the m6A modification of AKR1B10

Comprehensive Analysis of Differentially Expressed Profiles of mRNA N6-Methyladenosine in Colorectal Cancer

Role of m6A writers, erasers and readers in cancer

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