A pancancer analysis of the oncogenic role of ZNRF2 in human tumours.

Finding effective treatments for cancer requires a thorough understanding of how it develops and progresses. Recent research has revealed the crucial role that Zinc and ring finger 2 (ZNRF2) play in the progression of non-small cell lung cancer (NSCLC) by controlling cell growth and death. However, a comprehensive analysis of ZNRF2's role in cancer as a whole has yet to be conducted. Our study sought to investigate the impact of ZNRF2 on diverse human tumours, as well as the molecular pathways involved, using databases such as TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) and the Human Protein Atlas (HPA), as well as several bioinformatic tools. Our findings indicate that ZNRF2 is generally expressed at higher levels in tumours than in normal tissues, and in some cancers, its levels correlate positively with disease stage, potentially predicting a poor prognosis for patients. We also discovered genetic changes in ZNRF2 among cancer patients, as well as its relationship with cancer-related fibroblasts, endothelial cells and immune cell infiltration. Additionally, we explored potential molecular mechanisms of ZNRF2 in tumours, finding that it increases in hepatocellular carcinoma (HCC) tissues and that inhibiting its expression through ZNRF2 siRNA can limit HepG2 cell proliferation. Overall, our study provides a comprehensive overview of ZNRF2's oncogenic roles across various cancers.

Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury.

Infiltration of polymorphonuclear neutrophils (PMNs) plays a central role in acute lung injury (ALI). The mechanisms governing PMN inflammatory responses, however, remain incompletely understood. Based on our recent study showing a non-metabolic role of pyruvate kinase type M2 (PKM2) in controlling PMN degranulation of secondary and tertiary granules and consequent chemotaxis, here we tested a hypothesis that Pkm2-deficient mice may resist ALI due to impaired PMN inflammatory responses. We found that PMN aerobic glycolysis controlled the degranulation of secondary and tertiary granules induced by fMLP and PMA. Compared to WT PMNs, Pkm2-deficient (Pkm2-/-) PMNs displayed significantly less capacity for fMLP- or PMA-induced degranulation of secondary and tertiary granules, ROS production, and transfilter migration. In line with this, myeloid-specific Pkm2-/- mice exhibited impaired zymosan-induced PMN infiltration in the peritoneal cavity. Employing an LPS-induced ALI mouse model, LPS-treated Pkm2-/- mice displayed significantly less infiltration of inflammatory PMNs in the alveolar space and a strong resistance to LPS-induced ALI. Our results thus reveal that PKM2 is required for PMN inflammatory responses and deletion of PKM2 in PMN leads to an impaired PMN function but protection against LPS-induced ALI.