Background
The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase‐like 1 (METTL1)‐regulated m
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G tRNA modification in bladder cancer (BC) remain obscure.
Results
In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi‐omics analysis reveals that METTL1‐mediated m
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G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells.
Conclusions
Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1‐m
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G‐EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment.
Primary insomnia (PIs) is highly prevalent and can lead to adverse socioeconomic impacts, but the underlying mechanism of its complex brain network impairment remains largely unknown. Functional studies are too few and diverse in methodology, which makes it difficult to glean general conclusions. To answer this question, we first used graph theory-based network analyse, together with seed-based functional connectivity approach, to characterize the topology architecture of whole-brain functional networks associated with PIs. Forty-eight subjects with PIs and 48 age/sex/education-matched good sleepers were recruited. We found PIs is associated with altered connection properties of intra-networks within the executive control network, default mode network and salience network, and inter-network between auditory language comprehension center and executive control network. These complex networks were correlated with negative emotions and insomnia severity in the PIs group. Altered connection properties of these network hubs appeared to be neural risk factors for neuropsychological changes of PIs, and might be used as potential neuroimaging markers to distinguish the PIs from the good sleepers. These findings highlight the role of functional connectivity in the pathophysiology of PIs, and may underlie the neural mechanisms of etiology of PIs.
The aim of the present study was to determine the association of the Forkhead box P3 (FoxP3) rs3761548 polymorphism with the risk of colorectal cancer (CRC). Polymorphism genotyping was detected with polymerase chain reaction-polyacrylamide gel electrophoresis (PCR-PAGE), and data revealed that the AA, AC, and the combined A variant genotype (AA+AC) conferred a significantly greater risk of CRC [OR (95% CI) = 2.806 (1.726-4.563), 1.54 (1.121-2.11), and 1.797 (1.344-2.404), respectively]. Moreover, the A allele of rs3761548 was observed to be associated with higher susceptibility of CRC [OR (95% CI) = 1.792 (1.424-2.254)]. Unfortunately, no significant association was observed between the two subgroups after stratification by clinical characteristics including age; gender; tumor size, growth pattern, or differentiation; lymph node metastasis; and TNM pathological stage. Thus, we concluded that the FoxP3 gene polymorphism contributes to CRC susceptibility in a Chinese population.
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