METTL5-mediated 18S rRNA mA modification promotes oncogenic mRNA translation and intrahepatic cholangiocarcinoma progression.

Intrahepatic cholangiocarcinoma (ICC) is a deadly cancer with rapid tumor progression. While hyperactive mRNA translation caused by mis-regulated mRNA or tRNA modifications promotes ICC development, the role of rRNA modifications remains elusive. Here, we found that 18S rRNA mA modification and its methyltransferase METTL5 were aberrantly upregulated in ICC and associated with poorer survival (log rank test, p < 0.

Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer.

Unlabelled: The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments.

Intratumoral erythroblastic islands restrain anti-tumor immunity in hepatoblastoma.

Erythroblastic islands (EBIs) are the specialized structures for erythropoiesis, but they have never been found functional in tumors. As the most common pediatric liver malignancy, hepatoblastoma (HB) requires more effective and safer therapies to prevent progression and the lifelong impact of complications on young children. However, developing such therapies is impeded by a lack of comprehensive understanding of the tumor microenvironment.

The activation of mTOR signalling modulates DNA methylation by enhancing DNMT1 translation in hepatocellular carcinoma.

Background: Both dysregulation of mechanistic target of rapamycin (mTOR) signalling and DNA methylation patterns have been shown to be closely associated with tumor progression and serve as promising targets for hepatocellular carcinoma (HCC) therapy. Although their respective roles in HCC have been extensively revealed, the existence of molecular interactions between them remains largely unknown.

Methods: The association of DNA methylation and mTOR signalling in HCC tissues and cell lines was assessed.

Targeting tumour-intrinsic N-methylguanosine tRNA modification inhibits MDSC recruitment and improves anti-PD-1 efficacy.

Objective: Intrahepatic cholangiocarcinoma (ICC) exhibits very low response rate to immune checkpoint inhibitors (ICIs) and the underlying mechanism is largely unknown. We investigate the tumour immune microenvironment (TIME) of ICCs and the underlying regulatory mechanisms with the aim of developing new target to inhibit tumour growth and improve anti-programmed cell death protein-1 (PD-1) efficacy.

Design: Tumour tissues from patients with ICC together with hydrodynamic ICC mouse models were employed to identify the key cell population in TIME of ICCs.

Eliminating METTL1-mediated accumulation of PMN-MDSCs prevents hepatocellular carcinoma recurrence after radiofrequency ablation.

Background And Aims: Radiofrequency ablation (RFA) is an important curative therapy in hepatocellular carcinoma (HCC), but recurrence rate remains as high as all the other HCC therapeutic modalities. Methyltransferase 1 (METTL1), an enzyme for m 7 G tRNA modification, was reported to promote HCC development. Here, we assessed the role of METTL1 in shaping the immunosuppressive tumor microenvironment after insufficient RFA (iRFA).

METTL1 promotes hepatocarcinogenesis via m G tRNA modification-dependent translation control.

Background: N -methylguanosine (m G) modification is one of the most common transfer RNA (tRNA) modifications in humans. The precise function and molecular mechanism of m G tRNA modification in hepatocellular carcinoma (HCC) remain poorly understood.

Methods: The prognostic value and expression level of m G tRNA methyltransferase complex components methyltransferase-like protein-1 (METTL1) and WD repeat domain 4 (WDR4) in HCC were evaluated using clinical samples and TCGA data.

Pretreatment of Grape Seed Proanthocyanidin Extract Exerts Neuroprotective Effect in Murine Model of Neonatal Hypoxic-ischemic Brain Injury by Its Antiapoptotic Property.

Grape seed proanthocyanidin extract (GSPE), an active component extracted from the grape, has been reported to demonstrate antioxidant, anti-inflammatory, anticancer, and antiapoptosis effects. However, little is known about the role of GSPE on neonatal hypoxic-ischemic (HI) brain injury. The aim of this study was to evaluate the neuroprotective effect of GSPE pretreatment on neonatal HI brain injury in mice.

Decreased expression of ubiquilin‑1 following neonatal hypoxia‑ischemic brain injury in mice.

Ubiquilin‑1 (Ubqln), a ubiquitin‑like protein, regulates degradation of misfolded proteins and has been reported to have a crucial role in multiple pathologic and physiologic conditions. The current study was undertaken to investigate the expression of Ubqln in the brain of a neonatal hypoxia‑ischemic (HI) brain injury model induced using the Rice method with some modifications. Mouse pups at postnatal day 7 day were used in this study.