METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma

Chang, Yuzhou; Chai, Rui‐Chao; Pang, Bo; Chang, Xin; An, Song Yuan; Zhang, Ke‐Nan; Jiang, Tao; Wang, Yong-Zhi

doi:10.1016/j.canlet.2021.04.020

Cited by 102 publications

(95 citation statements)

References 39 publications

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“…Studies have also reported on the key role of METTL3 in various cancers. METTL3 can regulate MALAT1 stabilization through m6A modification, and it activates NF-κB activity to promote the malignant progression of glioma [ 36 ]. METTL3 increases miR-1246 levels through m6A modification, thereby promoting non-small-cell lung cancer progression [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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Background Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. Methods Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. Results M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain–containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. Conclusions M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A–CRB3–Hippo pathway.

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Section: Discussionmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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“…Interestingly, one recent genome-wide analysis of lncRNA half-lives in humans revealed that RBP-lncRNA interactions mainly enhance the stability of lncRNA with only one exon [ 22 ]. Additionally, N6-methyladenosine (m6A) writers and erasers, as well as readers, are all RBPs that modulate m6A modification and function of lncRNAs [ 23 ], primarily by affecting their stability and changing their expression levels [ 24 , 25 , 26 ]. Recently, RBP has also been reported to regulate the transcription of lncRNA.…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Xie

Zhou

et al. 2022

Genes

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Long non-coding RNAs (lncRNAs) have been well known for their multiple functions in the tumorigenesis, development, and prognosis of breast cancer (BC). Mechanistically, their production, function, or stability can be regulated by RNA binding proteins (RBPs), which were also involved in the carcinogenesis and progression of BC. However, the roles and clinical implications of RBP-related lncRNAs in BC remain largely unknown. Therefore, we herein aim to construct a prognostic signature with RBP-relevant lncRNAs for the prognostic evaluation of BC patients. Firstly, based on the RNA sequencing data of female BC patients from The Cancer Genome Atlas (TCGA) database, we screened out 377 differentially expressed lncRNAs related to RBPs. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were then performed to establish a prognostic signature composed of 12-RBP-related lncRNAs. Furthermore, we divided the BC patients into high- and low-risk groups by the prognostic signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that of the low-risk group. Moreover, the 12-lncRNA signature exhibited independence in evaluating the prognosis of BC patients. Additionally, a functional enrichment analysis revealed that the prognostic signature was associated with some cancer-relevant pathways, including cell cycle and immunity. In summary, our 12-lncRNA signature may provide a theoretical reference for the prognostic evaluation or clinical treatment of BC patients.

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“…They also further confirmed through in vivo and in vitro experiments that METTL3 can enhance the stability of MALAT1 through m6A modification and increase the expression level of MALAT1, which can activate NF-κB. This leads to the malignant progression of IDH wild-type glioma [ 53 ].…”

Section: Introductionmentioning

confidence: 91%

Interaction between m6A methylation and noncoding RNA in glioma

Tao

Wen

et al. 2022

Cell Death Discov.

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Glioma is considered to be the most common brain malignancy in the central nervous system. At present, the aetiology of glioma is not clear. Due to its rapidly growth and easily recurrence, the prognosis of patients with glioma is very poor. N6-methyladenosine (m6A) methylation is an internal reversible modification in most RNAs, including messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). Recent studies have shown that the m6A regulators are abnormal expressed, and are extensively involved in the progression of glioma by targeting ncRNAs. Moreover, as the most important epigenetic regulators, ncRNAs can also affect the function of m6A regulators in glioma. This review summarized the expression and function of certain common m6A regulators in glioma. Also, the current review sum up the mutual interactions between m6A regulators and ncRNAs in glioma.

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METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma

Cited by 102 publications

References 39 publications

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Interaction between m6A methylation and noncoding RNA in glioma

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