METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN

Qing, Tian; Zhang, Meifang; Zeng, Jinsheng; Luo, Rong-guang; Wen, Yang; Chen, Jun; Gan, Liugen; Xiong, Jianping

doi:10.1007/s00109-019-01830-9

Cited by 104 publications

(87 citation statements)

References 30 publications

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“…that CINP was identified through genome-wide association and large-scale follow-up analyses as one of the 16 new loci affecting lung function ( 38 ). In a study published by Tian et al., METTL1 was reported to be correlated with poor survival of HCC patients and enhance progression of hepatocellular carcinoma via PTEN ( 39 ). PWP2 belonged to the WD family and was indispensable to the assembly of 90S pre-ribosomal particle.…”

Section: Discussionmentioning

confidence: 99%

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

Zhou

et al. 2021

Front. Oncol.

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As a CRISPR-Cas9-based tool to help scientists to investigate gene functions, Cancer Dependency Map genes (CDMs) include an enormous series of loss-of-function screens based on genome-scale RNAi. These genes participate in regulating survival and growth of tumor cells, which suggests their potential as novel therapeutic targets for malignant tumors. By far, studies on the roles of CDMs in gastric adenocarcinoma (GA) are scarce and only a small fraction of CDMs have been investigated. In the present study, datasets of the differentially expressed genes (DEGs) were extracted from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which differentially expressed CDMs were determined. Functions and prognostic significance of these verified CDMs were evaluated using a series of bioinformatics methods. In all, 246 differentially expressed CDMs were determined, with 147 upregulated and 99 downregulated. Ten CDMs (ALG8, ATRIP, CCT6A, CFDP1, CINP, MED18, METTL1, ORC1, TANGO6, and PWP2) were identified to be prognosis-related and subsequently a prognosis model based on these ten CDMs was constructed. In comparison with that of patients with low risk in TCGA training, testing and GSE84437 cohort, overall survival (OS) of patients with high risk was significantly worse. It was then subsequently demonstrated that for this prognostic model, area under the ROC (receiver operating characteristic) curve was 0.771 and 0.697 for TCGA training and testing cohort respectively, justifying its reliability in predicting survival of GA patients. With the ten identified CDMs, we then constructed a nomogram to generate a clinically practical model. The regulatory networks and functions of the ten CDMs were then explored, the results of which demonstrated that as the gene significantly associated with survival of GA patients and Hazard ratio (HR), PWP2 promoted in-vitro invasion and migration of GA cell lines through the EMT signaling pathway. Therefore, in conclusion, the present study might help understand the prognostic significance and molecular functions of CDMs in GA.

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Section: Discussionmentioning

confidence: 99%

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

Zhou

et al. 2021

Front. Oncol.

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“…In addition, METTL14 and METTL3 play oncogenic roles in hepatocellular carcinomas (HCCs) (7). METTL1 up-regulation correlates with poor prognosis for patients with HCC and with HCC progression (12). It has been shown that METTL1 catalyzes 7-methylguanosine (m 7 G) formation in microRNAs (15) and transfer RNA (tRNAs) (10).…”

Section: Introductionmentioning

confidence: 99%

“…Different types of RNA methylations can be catalyzed by a large family of methyltransferase-like proteins (METTLs) that contain characterized as well as many predicted methyltransferases ( 11 ). Multiple METTL proteins have been implicated in different types of cancers ( 7 , 12 ). METTL3, in a complex with its interaction partner METTL14 ( 6 ), catalyzes N6-methyladenosine (m 6 A) in mRNAs and noncoding RNAs ( 13 ) and can promote oncogene expression and cancer cell growth in leukemia ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

METTL6 is a tRNA m ³ C methyltransferase that regulates pluripotency and tumor cell growth

Ignatova

Kaiser

et al. 2020

Sci. Adv.

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Recently, covalent modifications of RNA, such as methylation, have emerged as key regulators of all aspects of RNA biology and have been implicated in numerous diseases, for instance, cancer. Here, we undertook a combination of in vitro and in vivo screens to test 78 potential methyltransferases for their roles in hepatocellular carcinoma (HCC) cell proliferation. We identified methyltransferase-like protein 6 (METTL6) as a crucial regulator of tumor cell growth. We show that METTL6 is a bona fide transfer RNA (tRNA) methyltransferase, catalyzing the formation of 3-methylcytidine at C32 of specific serine tRNA isoacceptors. Deletion of Mettl6 in mouse stem cells results in changes in ribosome occupancy and RNA levels, as well as impaired pluripotency. In mice, Mettl6 knockout results in reduced energy expenditure. We reveal a previously unknown pathway in the maintenance of translation efficiency with a role in maintaining stem cell self-renewal, as well as impacting tumor cell growth profoundly.

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“…Decreased LRRC75A antisense RNA 1 (LRRC75A-AS1) plays an anti-tumor role in the tumorigenesis and progression of CRC, which may serve as a diagnostic marker in CRC [30]. Upregulated METTL1 is related to unfavorable outcomes in hepatocellular carcinoma, and METTL1 contributes to cell proliferation and migration in the tumor by inhibiting PTEN signaling [31]. Several highest-ranking genes (including TADA2B) are selected by RNAi Gene Enrichment Ranking algorithm, and their loss contributes to vemurafenib resistance in melanoma [32].…”

Section: Discussionmentioning

confidence: 99%

CA9 is an important molecular marker for the prognosis of osteosarcoma patients

Chen

Wang

et al. 2020

Preprint

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Background As a common malignant bone tumor, osteosarcoma (OS) progresses rapidly and recurs easily. This study is aimed to build a risk score system for OS patients. Methods From The Cancer Genome Atlas and Gene Expression Omnibus databases, the RNA-seq data of OS (the training set) and GSE39055 (the validation sets) separately were obtained. Combined with limma package, the differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) between recurrence and non-recurrence groups were analyzed. After the RNAs correlated with independent prognosis were screened using survival package, risk score systems were constructed and the optimal one was selected. For the independent clinical prognostic factors identified by survival package, stratification analysis was conducted. Using Gene Set Enrichment Analysis, pathways were enriched for the differentially expressed genes (DEGs) between high and low risk groups. Results For recurrence and non-recurrence groups, 319 DE-mRNAs and 14 DE-lncRNAs were identified. Subsequently, 10 DE-mRNAs (including ALDH1A1, CA9, GMDS, LCMT2, LRRC75A, METTL1, RAB29, TADA2B, TDRD7, and TIGD2) and eight DE-lncRNAs were found to be correlated with independent prognosis. From the four risk score systems, the mRNA expression status-based risk score system was selected as the optimal one. Among the three independent clinical prognostic factors, age and recurrence were significantly related to overall survival in high risk group. Additionally, vascular smooth muscle contraction, and glycine, serine and threonine metabolism were enriched for the DEGs between high and low risk groups. Conclusion The mRNA expression status-based risk score system might be devoted to predict the prognosis of OS patients.

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METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN

Cited by 104 publications

References 30 publications

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

METTL6 is a tRNA m ³ C methyltransferase that regulates pluripotency and tumor cell growth

CA9 is an important molecular marker for the prognosis of osteosarcoma patients

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METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN

Cited by 104 publications

References 30 publications

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma

METTL6 is a tRNA m 3 C methyltransferase that regulates pluripotency and tumor cell growth

CA9 is an important molecular marker for the prognosis of osteosarcoma patients

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METTL6 is a tRNA m ³ C methyltransferase that regulates pluripotency and tumor cell growth