Identification of zinc finger MIZ-type containing 2 as an oncoprotein enhancing NAD-dependent protein deacetylase sirtuin-1 deacetylase activity to regulate Wnt and Hippo pathways in non-small-cell lung cancer.

被引量：- 发表：1970

MicroRNAs in metabolism for precision treatment of lung cancer.

The dysregulation of miRNAs in lung cancer has been extensively documented, with specific miRNAs acting as both tumor suppressors and oncogenes, depending on their target genes. Recent research has unveiled the regulatory roles of miRNAs in key metabolic pathways, such as glycolysis, the tricarboxylic acid cycle, fatty acid metabolism, and autophagy, which collectively contribute to the aberrant energy metabolism characteristic of cancer cells. Furthermore, miRNAs are increasingly recognized as critical modulators of the tumor microenvironment, impacting immune response and angiogenesis. This review embarks on a comprehensive journey into the world of miRNAs, unraveling their multifaceted roles, and more notably, their emerging significance in the context of cancer, with a particular focus on lung cancer. As we navigate this extensive terrain, we will explore the fascinating realm of miRNA-mediated metabolic rewiring, a phenomenon that plays a pivotal role in the progression of lung cancer and holds promise in the development of novel therapeutic strategies.

被引量：- 发表：1970

Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis.

Glucokinase (GCK), a key enzyme in glucose metabolism, plays a central role in glucose sensing and insulin secretion in pancreatic β-cells, as well as glycogen synthesis in the liver. Mutations in the GCK gene have been associated with various monogenic diabetes (MD) disorders, including permanent neonatal diabetes mellitus (PNDM) and maturity-onset diabetes of the young (MODY), highlighting its importance in maintaining glucose homeostasis. Additionally, GCK gain-of-function mutations lead to a rare congenital form of hyperinsulinism known as hyperinsulinemic hypoglycemia (HH), characterized by increased enzymatic activity and increased glucose sensitivity in pancreatic β-cells. This review offers a comprehensive exploration of the critical role played by the GCK gene in diabetes development, shedding light on its expression patterns, regulatory mechanisms, and diverse forms of associated monogenic disorders. Structural and mechanistic insights into GCK's involvement in glucose metabolism are discussed, emphasizing its significance in insulin secretion and glycogen synthesis. Animal models have provided valuable insights into the physiological consequences of GCK mutations, although challenges remain in accurately recapitulating human disease phenotypes. In addition, the potential of human pluripotent stem cell (hPSC) technology in overcoming current model limitations is discussed, offering a promising avenue for studying GCK-related diseases at the molecular level. Ultimately, a deeper understanding of GCK's multifaceted role in glucose metabolism and its dysregulation in disease states holds implications for developing targeted therapeutic interventions for diabetes and related disorders.

被引量：- 发表：1970

Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway.

Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin.

被引量：- 发表：1970

Lysosome quality control in health and neurodegenerative diseases.

Lysosomes are acidic organelles involved in crucial intracellular functions, including the degradation of organelles and protein, membrane repair, phagocytosis, endocytosis, and nutrient sensing. Given these key roles of lysosomes, maintaining their homeostasis is essential for cell viability. Thus, to preserve lysosome integrity and functionality, cells have developed a complex intracellular system, called lysosome quality control (LQC). Several stressors may affect the integrity of lysosomes, causing Lysosomal membrane permeabilization (LMP), in which membrane rupture results in the leakage of luminal hydrolase enzymes into the cytosol. After sensing the damage, LQC either activates lysosome repair, or induces the degradation of the ruptured lysosomes through autophagy. In addition, LQC stimulates the de novo biogenesis of functional lysosomes and lysosome exocytosis. Alterations in LQC give rise to deleterious consequences for cellular homeostasis. Specifically, the persistence of impaired lysosomes or the malfunctioning of lysosomal processes leads to cellular toxicity and death, thereby contributing to the pathogenesis of different disorders, including neurodegenerative diseases (NDs). Recently, several pieces of evidence have underlined the importance of the role of lysosomes in NDs. In this review, we describe the elements of the LQC system, how they cooperate to maintain lysosome homeostasis, and their implication in the pathogenesis of different NDs.

被引量：- 发表：1970