PLA2G2D fosters angiogenesis in non-small cell lung cancer through aerobic glycolysis.

Non-small cell lung cancer (NSCLC) stands prominent among the prevailing and formidable oncological entities. The immune and metabolic-related molecule Phospholipase A2, group IID (PLA2G2D) exerts promotional effects on tumor progression. However, its involvement in cancer angiogenesis remains elusive. Therefore, this investigation delved into the functional significance of PLA2G2D concerning angiogenesis in NSCLC. This study analyzed the expression and enriched pathways of PLA2G2D in NSCLC tissues through bioinformatics analysis, and measured the expression of PLA2G2D in NSCLC cells using qRT-PCR and western blot (WB). Subsequently, the viability and angiogenic potential of NSCLC cells were assessed employing CCK-8 and angiogenesis assays, respectively. The expression profile of angiogenic factors was analyzed through WB. Finally, the expression of glycolysis pathway-related genes, extracellular acidification rate and oxygen consumption rate, and the levels of pyruvate, lactate, citrate, and malate were analyzed in NSCLC cells using qRT-PCR, Seahorse XF 96, and related kits. Bioinformatics analysis revealed the upregulation of PLA2G2D in NSCLC tissues and its association with VEGF and glycolysis signaling pathways. Molecular and cellular experiments demonstrated that upregulated PLA2G2D promoted the viability, angiogenic ability, and glycolysis pathway of NSCLC cells. Rescue assays revealed that the effects of high expression of PLA2G2D on the viability, angiogenic ability, and glycolysis of NSCLC cells were weakened after the addition of the glycolysis inhibitor 2-DG. In summary, PLA2G2D plays a key role in NSCLC angiogenesis through aerobic glycolysis, displaying great potential as a target for anti-angiogenesis therapy.

Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model.

We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.

Inhibition of RXRA-mediated PLA2G2A improves delirium in COPD mice by regulating endoplasmic reticulum stress pathway and inhibiting cell apoptosis.

Delirium is a common psychiatric complication of chronic obstructive pulmonary disease (COPD). The relief of delirium is considered one of the beneficial ways to treat COPD. However, there are currently no specific drugs that alleviate delirium in COPD patients. Our research aimed to elucidate the specific mechanisms underlying delirium in COPD mice, while also seeking more effective therapeutic targets. In our study, bioinformatics analysis and qRT PCR were used to identify key factors in the development of delirium in COPD animal models. Open field and elevated plus maze tests were used to detect delirium in mice. Tunel staining and HE staining were used to analyze the apoptosis of mouse hippocampus cells. EdU and CCK-8 experiments were used to analyze PC-12 cells vitality and proliferation. JASPAR online database, dual luciferase reporting experiments, ChIP experiments, and IF staining were used to analyze the interaction between RXRA and PLA2G2A. RXRA is highly expressed in the brain tissue of COPD mice with delirium symptoms. The downregulation of RXRA inhibits the delirium state in COPD mice. This is mainly due to the reduction of endoplasmic reticulum stress and cell apoptosis by inhibiting the expression of RXRA. In addition, we also confirmed that RXRA is a transcription factor of PLA2G2A. RXRA has an inhibitory effect on the expression of PLA2G2A. In vitro experiments have confirmed that inhibition of the RXRA/PLA2G2A axis reduces cell apoptosis, thereby alleviating the occurrence and development of delirium in COPD mice. Inhibition of the RXRA/PLA2G2A axis reduces endoplasmic reticulum stress and cell apoptosis. This process alleviates the development of delirium in COPD mice.