ALYREF-mediated RNA 5-Methylcytosine modification Promotes Hepatocellular Carcinoma Progression Via Stabilizing EGFR mRNA and pSTAT3 activation.

5-Methylcytosine (m5C) is one of the most ubiquitous modifications of mRNA and contributes to cancer pathogenesis. Aly/REF export factor (ALYREF), an m5C reader, is associated with the prognosis of liver hepatocellular carcinoma (LIHC). However, the effects of ALYREF on the progression of LIHC and the underlying molecular mechanisms remains elusive. Through an analysis of an online database and 3 independent LIHC cohorts, we found that ALYREF was markedly elevated in human liver cancer tissues and was significantly correlated with LIHC clinicopathological parameters, including Ki67+ cell rate, high-grade TNM stage, and poor prognosis. Several experiments were conducted to investigate the molecular basis and functional role of ALYREF-related progression in this study. ALYREF could enhance LIHC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and tumor formation in vivo. Mechanistically, ALYREF promoted the progression of human LIHC through EGFR pathways. Furthermore, ALYREF could directly bind to the m5C modification site of EGFR 3' untranslated region (3' UTR) to stabilize EGFR mRNA. Collectively, ALYREF played a crucial oncogenic role in LIHC via the stabilization of EGFR mRNA and subsequent activation of the STAT3 signaling pathway. Our results may help to elucidate the potential mechanisms of ALYREF-induced m5C modification in the progression of human LIHC.

The association between serum vitamin A and NAFLD among US adults varied in different BMI groups: a cross-sectional study.

Background and aims: The association between serum vitamin A (VA) and non-alcoholic fatty liver disease (NAFLD) has not been adequately studied. This study aimed to evaluate the association between them in different BMI groups among US adults. Methods: A cross-sectional study was performed using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets (N = 4.723). Linear/logistic regression, interaction effect and mediation analyses were adopted to analyze the association. Results: NAFLD tended to be more prevalent in adults in the middle and high tertiles of serum VA than in those in the low tertile of serum VA (OR [95% CI], 1.17 [0.94, 1.45] and 1.43 [1.16, 1.75]). In the sensitivity analysis, subjects in the middle or high tertile of serum VA had 10% (OR, 1.10 [0.88, 1.39] and 31% (OR, 1.31 [1.09, 1.58]) higher odds of NAFLD than those in the low tertile of serum VA. In the normal weight group, higher serum VA was associated with 125% and 333% higher odds of NAFLD in the middle and high tertiles, respectively, (OR, 2.25 [1.46, 3.48] and 4.33 [2.43, 7.69]) compared with the low tertile serum VA group. However, serum VA and NAFLD were not significantly associated with the obese group. Among different BMI groups (<30 compared with ≥30), serum triglycerides and insulin resistance mediated the association between VA and NAFLD in adults to varying degrees. Conclusions: In the weighted survey, serum VA was positively associated with the degree of NAFLD, especially in the non-obese population.

Research on THRβ gene mutation in a patient with thyroid hormone resistance syndrome using whole-exome sequencing / 中华内分泌代谢杂志

Objective:To assess clinical and genetic features in a patient with thyroid hormone resistance syndrome(RTH) and explore the pathogenic mechanism.Methods:The clinical data of the proband was collected. The genomic DNA was extracted from peripheral blood samples of the patients. The pathogenic variant was identified using whole-exome sequencing and confirmed by Sanger sequencing. Then the function of the mutation sites was detected by bioinformatics.Results:The patient presented with chest distress, palpitation, and persistent atrial fibrillation, along with elevated levels of serum free triiodothyronine(FT 3), free thyroxine(FT 4), and thyroid stimulating hormone(TSH), which suggested RTH clinically. The genetic analysis identified a heterozygous mutant of THRβ(c.1313G>A) gene at exon 8, which was a missense mutation causing the substitution of arginine to histidine at 438 position of the protein(p.R438H). Its inheritance pattern was unknown. This mutation was considered as a new one that had not been reported. Conclusion:A novel pathogenic THRβ gene mutation was found in the patient with RTH, which might be the cause of this disease. This variant c. 1313G>A is located in the ligand binding domain of THRβ, which might result in low protein activity.

Osteoglycin: An ECM Factor Regulating Fibrosis and Tumorigenesis.

The extracellular matrix (ECM) is made up of noncellular components that have special properties for influencing cell behavior and tissue structure. Small leucine-rich proteoglycans (SLRPs) are nonfibrillar ECM components that serve as structural scaffolds and signaling molecules. osteoglycin (OGN), a class III SLRP, is a ubiquitous ECM component that not only helps to organize the extracellular matrix but also regulates a number of important biological processes. As a glycosylated protein in the ECM, OGN was originally considered to be involved in fiber assembly and was reported to have a connection with fibrosis. In addition to these functions, OGN is found in a variety of cancer tissues and is implicated in cellular processes linked to tumorigenesis, including cell proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT). In this review, we summarize the structure and functions of OGN as well as its biological and clinical importance in the context of fibrotic illness and tumorigenesis. This review aims to improve our understanding of OGN and provide some new strategies for the treatment of fibrosis and cancer.