METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

Li, Rong; Mu, Chunlai; Cao, Yundi; Fan, Yingrui

doi:10.21037/atm-22-3849

Cited by 8 publications

(9 citation statements)

References 27 publications

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“…Several studies investigating TMT1B’s effects have highlighted a role in the regulation of cell proliferation in cancer cells. Following the loss of TMT1B expression in thyroid cancer cells, a significant decrease in proliferation was found, similar to effects seen in non-small cell lung cancer, clear cell renal cancer, and glioma cells ( 4 , 21 – 23 , 26 – 29 , 32 , 33 , 50 ). Conversely, overexpression of TMT1B in thyroid cancer and lung adenocarcinoma cells significantly promoted cell proliferation ( 29 , 50 ).…”

Section: Functional Role Of Tmt1b In Cancersupporting

confidence: 67%

“…Later functional studies with purified proteins confirmed that TMT1B’s methyltransferase activity is SAM-dependent ( 13 , 16 , 17 ), while microscopy studies with cultured cells refined its subcellular localisation to the perinuclear face of the ER ( 13 , 17 , 18 ), and the surface of lipid droplets (LD) ( 18 , 19 ), rather than the Golgi body ( 18 , 20 ). Differential expression of TMT1B has been found to occur within several cancer types ( 4 ), including gliomas ( 21 – 25 ), non-small cell lung cancer ( 16 , 23 , 26 – 29 ), and acute myeloid leukemia ( 30 , 31 ). TMT1B has been proposed as a biomarker for many of these cancers since its increased transcription and protein abundance is frequently correlated with an advanced TNM (Tumour, Node, Metastasis) stage of tumour development and poor patient overall survival ( 21 – 27 , 29 , 31 – 36 ), risk of recurrence ( 35 ) and drug resistance ( 16 , 37 ).…”

Section: Introduction: Methyltransferases and The Mettl Familymentioning

confidence: 99%

“…Differential expression of TMT1B has been found to occur within several cancer types ( 4 ), including gliomas ( 21 – 25 ), non-small cell lung cancer ( 16 , 23 , 26 – 29 ), and acute myeloid leukemia ( 30 , 31 ). TMT1B has been proposed as a biomarker for many of these cancers since its increased transcription and protein abundance is frequently correlated with an advanced TNM (Tumour, Node, Metastasis) stage of tumour development and poor patient overall survival ( 21 – 27 , 29 , 31 – 36 ), risk of recurrence ( 35 ) and drug resistance ( 16 , 37 ). Despite these characterizations, the exact substrate of TMT1B, and its role in the various cancers where it is highly expressed, have not yet been defined.…”

Section: Introduction: Methyltransferases and The Mettl Familymentioning

confidence: 99%

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Defining the elusive oncogenic role of the methyltransferase TMT1B

Denford

Wilhelm

2023

Front. Oncol.

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Methyltransferases are enzymes fundamental to a wide range of normal biological activities that can become dysregulated during oncogenesis. For instance, the recent description of the methyltransferase-like (METTL) family of enzymes, has demonstrated the importance of the N6-adenosine-methyltransferase (m6A) modification in transcripts in the context of malignant transformation. Because of their importance, numerous METTL family members have been biochemically characterized to identify their cellular substrates, however some members such as METTL7B, recently renamed TMT1B and which is the subject of this review, remain enigmatic. First identified in the stacked Golgi, TMT1B is also localized to the endoplasmic reticulum as well as lipid droplets and has been reported as being upregulated in a wide range of cancer types including lung cancer, gliomas, and leukemia. Interestingly, despite evidence that TMT1B might act on protein substrates, it has also been shown to act on small molecule alkyl thiol substrates such as hydrogen sulfide, and its loss has been found to affect cellular proliferation and migration. Here we review the current evidence for TMT1B’s activity, localization, and potential biological role in the context of both normal and cancerous cell types.

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Section: Functional Role Of Tmt1b In Cancersupporting

confidence: 67%

Section: Introduction: Methyltransferases and The Mettl Familymentioning

confidence: 99%

Section: Introduction: Methyltransferases and The Mettl Familymentioning

confidence: 99%

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Defining the elusive oncogenic role of the methyltransferase TMT1B

Denford

Wilhelm

2023

Front. Oncol.

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“…Li et al. have reported that METTL7B is a biomarker for prognosis and promotes the metastasis of lung adenocarcinoma cells ( 41 ). Moreover, METTL7B is mainly involved in regulating immunity and ROS generation, which are two important biological processes in both HF and lung cancer ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Heart failure–related genes associated with oxidative stress and the immune landscape in lung cancer

Duan

et al. 2023

Front. Immunol.

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BackgroundLung cancer is a common comorbidity of heart failure (HF). The early identification of the risk factors for lung cancer in patients with HF is crucial to early diagnosis and prognosis. Furthermore, oxidative stress and immune responses are the two critical biological processes shared by HF and lung cancer. Therefore, our study aimed to select the core genes in HF and then investigate the potential mechanisms underlying HF and lung cancer, including oxidative stress and immune responses through the selected genes.MethodsDifferentially expressed genes (DEGs) were analyzed for HF using datasets extracted from the Gene Expression Omnibus database. Functional enrichment analysis was subsequently performed. Next, weighted gene co-expression network analysis was performed to select the core gene modules. Support vector machine models, the random forest method, and the least absolute shrinkage and selection operator (LASSO) algorithm were applied to construct a multigene signature. The diagnostic values of the signature genes were measured using receiver operating characteristic curves. Functional analysis of the signature genes and immune landscape was performed using single-sample gene set enrichment analysis. Finally, the oxidative stress–related genes in these signature genes were identified and validated in vitro in lung cancer cell lines.ResultsThe DEGs in the GSE57338 dataset were screened, and this dataset was then clustered into six modules using weighted gene co-expression network analysis; MEblue was significantly associated with HF (cor = −0.72, p < 0.001). Signature genes including extracellular matrix protein 2 (ECM2), methyltransferase-like 7B (METTL7B), meiosis-specific nuclear structural 1 (MNS1), and secreted frizzled-related protein 4 (SFRP4) were selected using support vector machine models, the LASSO algorithm, and the random forest method. The respective areas under the curve of the receiver operating characteristic curves of ECM2, METTL7B, MNS1, and SFRP4 were 0.939, 0.854, 0.941, and 0.926, respectively. Single-sample gene set enrichment analysis revealed significant differences in the immune landscape of the patients with HF and healthy subjects. Functional analysis also suggested that these signature genes may be involved in oxidative stress. In particular, METTL7B was highly expressed in lung cancer cell lines. Meanwhile, the correlation between METTL7B and oxidative stress was further verified using flow cytometry.ConclusionWe identified that ECM2, METTL7B, MNS1, and SFRP4 exhibit remarkable diagnostic performance in patients with HF. Of note, METTL7B may be involved in the co-occurrence of HF and lung cancer by affecting the oxidative stress immune responses.

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“…The use of METTL7B as a potential therapeutic target can improve the efficacy of EGFR inhibitors. METTL7B expression is also significantly higher in LUAD cancer tissues than in the paracancer tissues and is mainly distributed in the cytoplasm, significantly promoting LUAD metastasis [ 265 ]. RhoBTB1 and 2, members of the Rho GTPase family, regulating the expression of methyltransferases METTL7B and METTL7A, respectively; however, RhoBTB1 and 2 are often silent or mutate in a wide range of epithelial cell cancers, resulting in Golgi fragmentation-induced breast cancer cell invasion [ 266 ].…”

Section: Mettls In Tumor Chemotherapymentioning

confidence: 99%

Methyltransferase-like proteins in cancer biology and potential therapeutic targeting

Zhu

Ling

et al. 2023

J Hematol Oncol

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RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets.

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METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

Cited by 8 publications

References 27 publications

Defining the elusive oncogenic role of the methyltransferase TMT1B

Defining the elusive oncogenic role of the methyltransferase TMT1B

Heart failure–related genes associated with oxidative stress and the immune landscape in lung cancer

Methyltransferase-like proteins in cancer biology and potential therapeutic targeting

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