METTL7B promotes migration and invasion in thyroid cancer through epithelial-mesenchymal transition

Ye, Danrong; Jiang, Yang; Sun, Yihan; Li, Yuefeng; Cai, Yefeng; Wang, Qingxuan; Wang, Ouchen; Chen, Endong; Zhang, Xiaohua

doi:10.1530/jme-18-0261

Cited by 31 publications

(31 citation statements)

References 43 publications

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“…Previous study showed that METTL7B might serve as a biomarker for diagnosis and tumor progression in papillary thyroid carcinoma (Cai et al, 2018). METTL7B enhanced migration and invasion of thyroid carcinoma cells through promote TGF-b1-induced epithelial-mesenchymal transition (EMT) (Ye et al, 2019). In our study, we provide evidence showing that METTL7B is a potential therapeutic target for NSCLC.…”

Section: Discussionsupporting

confidence: 52%

METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer

Liu

Zhong

et al. 2020

Front. Pharmacol.

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Lung cancer remains a leading cause of cancer-associated mortality worldwide, however, molecular mechanisms underlying lung cancer tumorigenesis and progression remain unknown. Here, we report evidence showing that one member of the mammalian methyltransferase-like family (METTL), METTL7B, is a potential molecular target for treatment of non-small cell lung cancer (NSCLC). METTL7B expression was elevated in the majority of NSCLC comparing to normal tissues. Increased expression of METTL7B contributed to advanced stages of tumor development and poor survival in NSCLC patients. Lentivirus-mediated shRNA silencing of METTL7B suppressed proliferation and tumorigenesis of cancer cells in vitro and in vivo. Investigation on gene expression profiles of NSCLC cells revealed that abundant cell cycle related genes were downregulated in the absence of METTL7B. Pathway enrichment analysis indicated that METTL7B participated in cell cycle regulation. Notably, CCND1, a key regulator for G1/S transition, was significantly decreased with the depletion of METTL7B, resulting in G0/G1 arrest, indicating that METTL7B is critical for cell cycle progression. Taken together, our findings implicate that METTL7B is essential for NSCLC development and progression. METTL7B might serve as a potential therapeutic target for NSCLC.

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Section: Discussionsupporting

confidence: 52%

METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer

Liu

Zhong

et al. 2020

Front. Pharmacol.

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“…Endogenous thiols such as glutathione and cysteine or classic probe substrates of other known small molecule S -, N -, and O - methyltransferases were not substrates for METTL7B. Our results unequivocally demonstrate, and for the first time, that METTL7B, a protein implicated in several disease states, is an alkyl thiol methyltransferase(3–5). Identifying the catalytic function of METTL7B will enable future pharmacological research in disease pathophysiology where METTL7B expression and H 2 S levels can potentially alter the redox state and growth cycle of cells.…”

supporting

confidence: 49%

“…To date, the catalytic function of methyltransferase-like protein 7B (METTL7B) was unknown despite being implicated in several disease states. Specifically, METTL7B gene expression is significantly altered in kidney disease, acute respiratory distress syndrome, and numerous cancers, including breast, non-small cell lung, thyroid, and ovarian(3–5, 14–17). METTL7B expression appears to be responsive to inflammation signaling pathways via JAK1(18, 19).…”

Section: Introductionmentioning

confidence: 99%

HumanMETTL7BEncodes an Alkyl Thiol Methyltransferase that Methylates Hydrogen Sulfide

Maldonato

Totah

2020

Preprint

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Paragraph/Abstract: 27Methyltransferase-like protein 7B (METTL7B) is implicated in tumor growth and 28 progression while gene expression is upregulated in several different disease states such as 29 72 including hydrogen sulfide, captopril, 7α-thiospironolactone, D-and L-penicillamine, and the 73 active metabolites of prasugrel, and ziprasidone (1, 2,(23)(24)(25)(26)(27). However, despite numerous 74 attempts, researchers have not successfully identified the TMT gene or protein (28-31). 75Our preliminary approach to identify TMT expanded on earlier research which attempted 76 to purify TMT from rat liver microsomes using a number of chromatographic steps (28, 31). 77After significant increases in TMT specific activity, preliminary non-targeted proteomic 78 experiments were conducted to identify potential methyltransferase proteins in the TMT-active 79 fractions. The major candidate protein in active fractions was identified as rat METTL7B which 80 was also localized to the endoplasmic reticulum (Extended Data Table 1). Rat and human 81 METTL7B share 83% sequence homology, which suggests a conserved function. Subsequent 82 experiments modulating the expression of human METTL7B in two cell lines also altered 83 captopril methylation, a known TMT substrate. Once identified, we cloned, recombinantly84 expressed, and purified human full length METTL7B in E. coli and conducted small molecule 85 substrate screening with the purified protein. The activity screens confirmed that METTL7B 86 specifically catalyzes SAM-dependent methylation of aliphatic thiol compounds, including 87 hydrogen sulfide, in a time and protein concentration dependent manner. No methylation was 88 observed with classic probe substrates of other known small molecule S-, N-, and O-89 methyltransferases(32-36) or endogenous thiols such as cysteine or glutathione.90 91 92 93 109 B) Methylation of captopril activity significantly decreased in HepG2 cells treated with METTL7B siRNA compared 110 to control cells. C) HeLa cells treated with a METTL7B overexpression plasmid showed ~ 1,000-fold increase in 111 METT7B gene expression compared to control cells transfected with an empty expression vector. D) HeLa cells 112transfected with the METTL7B expression vector showed a 10-fold increase in captopril methylation activity 113 compared to negative control cells. E) FLAG-tagged METTL7B expression is only observed in cells treated with 114 the METTL7B overexpression plasmid compared to controls (Lanes 2 and 1 respectively). ß-actin was used as a 115 loading control. All data is presented as the mean ± standard deviation. Individual data points from two (A, C, and 116 D) or three (B) experiments are plotted. Significance was determined using unpaired two-tailed t test.

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“…In the study of non-small cell lung cancer (NSCLC), METTL7B is the target of NSCLC treatment and is involved in the regulation of the tumor cell cycle ( Liu et al, 2020 ). In addition, METTL7B may also activate TGFβ1 and induce EMT in thyroid cancer ( Ye et al, 2019 ). Our results also showed that METTL7B is highly expressed in both the metastasis group and the high-risk group, and is related to signaling pathways, such as the WNT and MAPK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Validation of a Comprehensive Prognostic Model for Patients With HNSCC Metastasis

Shen

et al. 2021

Front. Genet.

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ObjectiveTo identify biomarkers related to head and neck squamous cell carcinoma (HNSCC) metastasis and establish a prognostic model for patients with HNSCC.MethodsHNSCC mRNA expression data of metastasis and non-metastatic samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. After screening the differentially expressed genes (DEGs) in the two datasets, a prognostic model, including clinical factors and biomarkers, was established, and verified in 36 samples of HNSCC by quantitative real-time transcription (qRT)-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene sets enrichment analysis (GSEA) were consulted to explore the functions of the DEGs.ResultsIn total, 108 DEGs were identified. GSEA, GO, and KEGG analyses showed that these DEGs were mainly involved in the proliferation and metastasis of HNSCC. Six genes that were significantly related to metastasis, immune cell infiltration and prognosis were further identified to construct a prognostic gene signature. The reliability of the gene signature was verified in 36 samples of HNSCC. A prognostic model, including tumor stage, risk level, and a nomogram for prediction were further established. Receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), C-index, and calibration plots showed that the model and nomogram perform well.ConclusionWe constructed a six-gene signature and a nomogram with high performance in predicting the prognosis of patients with HNSCC metastasis.

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METTL7B promotes migration and invasion in thyroid cancer through epithelial-mesenchymal transition

Cited by 31 publications

References 43 publications

METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer

METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer

HumanMETTL7BEncodes an Alkyl Thiol Methyltransferase that Methylates Hydrogen Sulfide

Establishment and Validation of a Comprehensive Prognostic Model for Patients With HNSCC Metastasis

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