IFIH1-mediated post-transcriptional regulation of PTTG1 promotes proliferation and affects PHA-848125 sensitivity and prognosis in oropharyngeal carcinoma.

The pituitary tumor-transforming gene 1 (PTTG1) is an oncogene involved in chromosomal segregation, DNA repair, apoptosis, and metabolism. PTTG1 can be used for clinical diagnosis and treatment and is a potential target for oropharyngeal carcinoma. The proliferation and viability of Cal27 and FaDu cells were assessed using the CCK-8 assay. Real-time PCR and western blotting, respectively, were used to analyze the mRNA and protein expression levels of PTTG1 and IFIH1. The interaction between PTTG1 mRNA and the translational regulatory protein IFIH1 was analyzed using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. PTTG1 protein was significantly overexpressed in oropharyngeal carcinoma, whereas PTTG1 mRNA was not. We hypothesized that a translation regulatory protein plays a post-transcriptional role in PTTG1. The IFIH1 protein specifically bound to the 42-52 nt region of PTTG1 mRNA, promoted the translation of PTTG1, and promoted the proliferation of oropharyngeal cancer cells. Administration of the PTTG1 inhibitor PHA-848125 and silencing of IFIH1 synergistically decreased the expression of PTTG1, inhibited the proliferation of oropharyngeal cancer cells, and indicated a good prognosis. We found that the IFIH1-PTTG1 axis could regulate the PHA-848125 response and functionally mediate inter-individual oropharyngeal cancer susceptibility and prognosis. This study aimed to confirm the upstream regulatory genes of PTTG1 and further investigate the specific interactions in this signaling pathway, which will provide a new approach for the treatment of oropharyngeal carcinoma.

Application of ultrasound elastography and radiomic for predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma.

Objective: This study aims to combine ultrasound (US) elastography (USE) and radiomic to predict central cervical lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: A total of 204 patients with 204 thyroid nodules who were confirmed with PTMC and treated in our hospital were enrolled and randomly assigned to the training set (n = 142) and the validation set (n = 62). US features, USE (gender, shape, echogenic foci, thyroid imaging reporting and data system (TIRADS) category, and elasticity score), and radiomic signature were employed to build three models. A nomogram was plotted for the combined model, and decision curve analysis was applied for clinical use. Results: The combined model (USE and radiomic) showed optimal diagnostic performance in both training (AUC = 0.868) and validation sets (AUC = 0.857), outperforming other models. Conclusion: The combined model based on USE and radiomic showed a superior performance in the prediction of CLNM of patients with PTMC, covering the shortage of low specificity of conventional US in detecting CLNM.

Effects of Scallop Mantle Toxin on Intestinal Microflora and Intestinal Barrier Function in Mice.

Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China's coastal areas and explore the impact of scallop mantle toxins (SMT) on intestinal barrier integrity and gut microbiota in mice. The Illumina MiSeq sequencing of V3-V4 hypervariable regions of 16S ribosomal RNA was employed to study the alterations in gut microbiota in the feces of SMT mice. The results showed that intestinal flora abundance and diversity in the SMT group were decreased. Compared with the control group, significant increases were observed in serum indexes related to liver, intestine, inflammation, and kidney functions among SMT-exposed mice. Accompanied by varying degrees of tissue damage observed within these organs, the beneficial bacteria of Muribaculaceae and Marinifilaceae significantly reduced, while the harmful bacteria of Enterobacteriaceae and Helicobacter were significantly increased. Taken together, this article elucidates the inflammation and glucose metabolism disorder caused by scallop mantle toxin in mice from the angle of gut microbiota and metabolism. SMT can destroy the equilibrium of intestinal flora and damage the intestinal mucosal barrier, which leads to glucose metabolism disorder and intestinal dysfunction and may ultimately bring about systemic toxicity.

LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1-166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.