Decapping enzymes STOP “cancer” ribosomes in their tracks

Mugridge, Jeffrey S.; Gross, John D.

doi:10.15252/embj.2018100801

Cited by 5 publications

(4 citation statements)

References 11 publications

(17 reference statements)

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“…Ribosomes take part in the synthesis of proteins, as the site of mRNA translation (12). Recently, increasing evidence has demonstrated that ribosomes can regulate cancer progression and drug reactions by 'alternative translation', which enables tumor cells to adapt to their environment in order to proliferate (13)(14)(15)(16). Methylation of ribosomal (r)RNA is the primary method to control protein synthesis (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma

Zhang

et al. 2020

Oncol Lett

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Hepatocellular carcinoma (HCC) is the sixth most common cancer and third most common cause of cancer-associated mortality worldwide. Hepatectomy and liver transplantation are the main treatments for early HCC. Immunotherapy and targeted therapy for advanced HCC have become increasingly popular; however, their clinical benefits are limited. Thus, identification of novel therapeutic targets for advanced HCC remains essential. Fibrillarin (FBL) is an essential nucleolar protein that catalyzes the 2′-O-methylation of ribosomal RNAs. Recently, experimental data have suggested that FBL can influence breast-cancer progression. However, the association between FBL expression and HCC remains known. In the present study, the UALCAN database was used to assess FBL mRNA expression in HCC. Immunohistochemistry analysis was performed to detect FBL protein expression in 139 patients with HCC. In addition, bioinformatic analysis was performed using the UALCAN, the Database for Annotation, Visualization and Integrated Discovery, cBioportal and TargetScan databases. Data were analyzed using Kaplan-Meier curves and the log-rank test, and a Cox proportional hazards regression model. The results demonstrated that FBL expression was significantly higher in tumor tissues compared with para-tumor tissues. Furthermore, high FBL expression was significantly associated with tumor diameter and advanced TNM stage in HCC. High FBL expression also predicted a shorter overall survival time and disease-free survival time in patients with HCC. Bioinformatics analysis demonstrated that FBL may be regulated by methylation modification. In addition, analyses of functional annotations using the Gene Ontology database indicated that FBL-related genes were predominantly enriched in DNA repair and proliferation-related cell-signaling pathways. Notably, high FBL expression signified larger tumor diameter, advanced tumor stage and a poor prognosis. Taken together, the results of the present study suggest that FBL may be a potential target for HCC treatment.

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Section: Introductionmentioning

confidence: 99%

Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma

Zhang

et al. 2020

Oncol Lett

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“…The Sankey diagram showed that AC018647.1, AL355472.3, and SALRNA1 are related to DCP2. DCP2 is a decapping enzyme that plays a significant role in the regulation of the cell cycle and proliferation ( Mugridge and Gross, 2018 ). DCP2 was found to promote lung cancer proliferation ( Zhang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Risk Model and Immune Signature of m7G-Related lncRNA Based on Lung Adenocarcinoma

et al. 2022

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Lung cancer is a major cause of cancer-related deaths globally, with a dismal prognosis. N7-methylguanosine (m7G) is essential for the transcriptional phenotypic modification of messenger RNA (mRNA) and long noncoding RNA (lncRNA). However, research on m7G-related lncRNAs involved in lung adenocarcinoma (LUAD) regulation is still limited. Herein, we aim to establish a prognostic model of m7G-related lncRNAs and investigate their immune properties. Eight prognostic m7G-related lncRNAs were identified using univariate Cox analysis. Six m7G-related lncRNAs were identified using LASSO-Cox regression analysis to construct risk models, and all LUAD patients in The Cancer Genome Atlas (TCGA) cohort was divided into low-risk and high-risk subgroups. The accuracy of the model was verified by Kaplan-Meier analysis, time-dependent receiver operating characteristic, principal component analysis, independent prognostic analysis, nomogram, and calibration curve. Further studies were conducted on the gene set enrichment and disease ontology enrichment analyses. The gene set enrichment analysis (GSEA) revealed that the high-risk group enriched for cancer proliferation pathways, and the enrichment analysis of disease ontology (DO) revealed that lung disease was enriched, rationally explaining the superiority of the risk model. Finally, we found that the low-risk group had higher immune infiltration and checkpoint expression. It can be speculated that the low-risk group has a better effect on immunotherapy. Susceptibility to antitumor drugs in different risk subgroups was assessed, and it found that the high-risk group showed high sensitivity to first-line treatment drugs for non-small cell lung cancer. In conclusion, a risk model based on 6 m7G-related lncRNAs can not only predict the overall survival (OS) rate of LUAD patients but also guide individualized treatment for these patients.

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“…[38,39] By decapping a subset of mRNAs, DCP2 plays an important role in cancer pathogenesis by affecting processes such as cell migration and apoptosis. [40][41][42][43][44] More interestingly, DCP2 is regulated at the post-transcriptional level rather than being transcriptionally silenced, and miRNAs are an effective way to down-regulate DCP2. DCP2 mRNA has a fairly long 3′-UTR of 7.2 kb that may contain many potential miRNA binding sites.…”

Section: Discussionmentioning

confidence: 99%

miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation

Zhang

Yan

et al. 2020

Preprint

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Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.

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Decapping enzymes STOP “cancer” ribosomes in their tracks

Cited by 5 publications

References 11 publications

Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma

Increased fibrillarin expression is associated with tumor progression and an unfavorable prognosis in hepatocellular carcinoma

Risk Model and Immune Signature of m7G-Related lncRNA Based on Lung Adenocarcinoma

miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation

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