Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment.
The ultrafast PWV is an effective and user-friendly method for evaluating carotid stiffness. The IMT and transducer type are factors influencing the ability to obtain an ultrafast PWV measurement.
Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
Background: Different delivery modes can affect the early pelvic floor function of puerpera, but there are no reports on the systematic evaluation of the effects of selective cesarean section delivery (CSD) and vaginal delivery (VD) on the pelvic floor function of puerpera.Methods: We searched for clinical controlled studies on the evaluation of pelvic floor function and performance after CSD and VD, published between 1 January 2010 and 1 August 2021, in the databases of PubMed, Embase, The Cochrane Library, and Web of Science. Literature was screened according to the inclusion and exclusion criteria. The quality of trials included in the studies was evaluated using the Cochrane Working Manual (5.3). Meta-analysis of the extracted data from the eligible articles was performed using Review Manager 5.3 software. The heterogeneity was assessed by chi-square, and P<0.05 was considered statistically significant among groups.Results: A total of 3,704 parturient women were included in 10 articles, including 1,072 cases in the CSD group and 2,632 cases in the VD group. Meta-analysis showed that pelvic floor muscle strength {mean difference (MD) [95% confidence interval (CI)]: −12.51 (−17.10 to −7.91); Z=5.34; P<0.00001} and bladder neck strength decreases in the CSD group [standardized mean difference (SMD) (95% CI): 1.01 (0.73 to 1.29); Z=7.08; P<0.00001] were higher than those in the VD group. In addition, the maximum urine flow [MD (95% CI): −6.86 (−9.32 to −4.39); Z=5.46; P<0.00001], bladder angle [MD (95% CI): −3.82 (−4.54 to −3.11); Z=10.46; P<0.00001], stress urinary incontinence (SUI) rate [relative risk (RR) (95% CI): 0.56 (0.35 to 0.88); Z=2.52; P=0.01], and pelvic floor organ prolapse rate [odds ratio (OR) (95% CI): 0.29 (0.09 to 0.89); Z=2.17; P=0.03] were lower than VD group, and the differences were significant (P<0.05).
Conclusions:Selective CSD can reduce the injury of pelvic floor muscle during delivery to a certain extent, and reduce the incidence of SUI and pelvic floor organ prolapse in early puerpera; however, such impacts cannot be completely avoided.
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