METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Jiang, Zhipeng; Wu, Yin; Zhu, Hecheng; Tan, Jun; Guo, Youwei; Xin, Zhaoqi; Zhou, Quanwei; Cao, Yudong; Wu, Zhaoping; Kuang, Yirui; Li, Can; Xie, Dongcheng; Huang, Hailong; Zhao, Ming; Jiang, Xingjun; Wang, Lei; Ren, Chao

doi:10.1186/s12935-021-02087-4

Cited by 19 publications

(17 citation statements)

References 41 publications

(58 reference statements)

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“…In one large-cohort multi-cancer, multiomics study, higher METTL7A expression was determined to have the most favorable survival across cancers compared to other METTLs (Campeanu et al, 2021). METTL7B , antithetically, is significantly upregulated across most cancers (Jiang et al, 2021). TMT1B1 regulates the epithelial-mesenchymal transition of thyroid cancer cells in the presence of TGF-β, an important regulator of cancer immunosuppression (Ye et al, 2019; Chen et al, 2021; Xiong et al, 2021); and in multiple cell lines, TMT1B1 promotes G1 to S phase transition in cancer cells (Liu et al, 2020; Li et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

METTL7A and METTL7B are responsible forS-thiol methyl transferase activity in liver

Russell

Chau

Shi

et al. 2022

Preprint

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S-Methylation of drugs containing thiol-moieties often alters their activity and results in detoxification. Historically, scientists attributed methylation of exogenous aliphatic and phenolic thiols to a putative S-adenosyl-L-methionine dependent membrane-associated phase II enzyme known as thiol methyltransferase (TMT). TMT has a broad substrate specificity and methylates the thiol metabolite of spironolactone, mertansine, ziprasidone, captopril, and the active metabolites of the thienopyridine pro-drugs, clopidogrel, and prasugrel. Despite TMT's role in the S-methylation of clinically relevant drugs, the enzyme(s) responsible for this activity remained unknown. We recently identified methyltransferase-like protein 7B (METTL7B) as an alkyl thiol-methyltransferase. METTL7B is an endoplasmic-reticulum-associated protein with similar biochemical properties and substrate specificity to TMT. Yet, the historic TMT inhibitor, 2,3-dichloro-a-methylbenzylamine (DCMB), has no effect on the activity of METTL7B, indicating that multiple enzymes contribute to TMT activity. Here we report that methyltransferase-like protein 7A (METTL7A), an uncharacterized member of the METTL7 family, also acts as a thiol-methyltransferase. METTL7A exhibits similar biochemical properties to TMT, including inhibition by DCMB (IC50 1.2 uM). Applying quantitative proteomics to human liver microsomes and gene modulation experiments in HepG2 and HeLa cells, we determined that TMT activity correlates closely with METTL7A and METTL7B protein levels. Furthermore, purification of a novel His-GST-tagged recombinant protein and subsequent activity experiments prove that METTL7A can selectively methylate exogenous thiol-containing substrates, including 7a-thiospironolactone, dithiothreitol, 4-chlorothiophenol, and mertansine. We conclude that the METTL7 family encodes for two enzymes, METTL7A and METTL7B, which we have renamed TMT1A1 and TMT1B1, respectively, that are responsible for TMT activity in liver microsomes.

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Section: Discussionmentioning

confidence: 99%

METTL7A and METTL7B are responsible forS-thiol methyl transferase activity in liver

Russell

Chau

Shi

et al. 2022

Preprint

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“…An EMT signature performs well in predicting the overall survival, and the model is associated with immune infiltration, proving its potential role in regulating immune status [ 16 ]. Additionally, other EMT-immune-related biomarkers, for example, LIPH, CDH11, SETBP1, and so on, also have prognostic value in different cancers [ 17 – 23 ]. However, they are far from sufficient, more biomarkers should be identified and verified.…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer

et al. 2022

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Colon cancer (CC) is a disease with high incidence and mortality rate. The interaction between epithelial-mesenchymal transition (EMT) and immune status has important clinical significance. We aim to identify EMT-immune-related prognostic biomarkers in colon cancer. The GEO2R and GEPIA 2.0 were utilized to calculate the differential expression genes between CC and normal mucosa. Immport, InnateDB and EMTome databases were used to define EMT-immune-related genes. We conducted batch prognostic analysis by TCGA data. The expression patterns were verified by multiple datasets and lab experiments. GEPIA 2.0 and TIMER 2.0 were utilized to analyze the correlation of the hub genes with EMT markers and immune infiltration. GeneMANIA, STRING, and Metascape were used for co-expression and pathway enrichment analysis. Finally, we established a signature by the method of multivariate Cox regression analysis. CDKN2A, CMTM8 and ILK were filtered out as prognostic genes. CDKN2A and CMTM8 were up-regulated, while ILK was down-regulated in CC. CDKN2A was positively correlated with infiltration of macrophages, Th2 cells, Treg cells, and negatively correlated with NK cells. CMTM8 was negatively correlated with CD8+ T cells, dendritic cells, and NK cells. ILK was positively correlated with CD8+ T cells and dendritic cells. Moreover, CDKN2A, CMTM8 and ILK were significantly correlated with EMT markers. The three genes could participate in the TGF-β pathway. The prognosis model established by the three hub genes was an independent prognosis factor, which can better predict the prognosis. CDKN2A, CMTM8 and ILK are promising prognostic biomarkers and may be potential therapeutic targets in colon cancer.

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“…The TMB represents the number of somatic gene mutations existed in the cancer cells [ 28 ]. MSI refers to genetic instability caused by impaired DNA MMR [ 29 ]. MMR maintains the integrity and stability of the whole genome by correcting DNA replication or recombination errors [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis

et al. 2023

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Background The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. Methods In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. Results ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. Conclusions This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.

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METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

Cited by 19 publications

References 41 publications

METTL7A and METTL7B are responsible forS-thiol methyl transferase activity in liver

METTL7A and METTL7B are responsible forS-thiol methyl transferase activity in liver

Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis

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