[ANXA8 Regulates Proliferation of Human Non-Small Lung Cancer Cells A549 via EGFR-AKT-mTOR Signaling Pathway].

Annexin A8 (ANXA8) is a member of the annexin family, which had been reported to regulate multiple cancer cellular processes including proliferation, metastasis and inflammation. However, the specific role of ANXA8 in lung cancer cell biology remains unknown. Our previous transcriptome study revealed that ANXA8 mRNA was downregulated in curcumin analog (MHMD) -treated human non-small lung cancer cells (A549 cell line). Here, we continued to study the ANXA8 expression in A549 cells using reverse transcription-quantitative PCR and Western blotting, compared with that in human normal bronchial epithelium cells (BE-AS-2B cell line). Overexpression of ANXA8 via transfection of pEGFP-ANXA8 recombinant vector contributed to the proliferation and migration of A549 cells. Moreover, the cell cycle protein cyclin E1 was upregulated in ANXA8-transfected A549 cells. Knockdown of ANXA8 using an RNA interference technique decreased A549 cell viability and restrained their migration in vitro. The expression levels of multiple cellular factors, including EGFR, PI3K, Akt, mTOR, p70S6K and 4EBP1, in the epidermal growth factor receptor (EGFR) signaling pathway were also altered by ANXA8 knockdown or overexpression in A549 cells, which confirmed the activation of the EGFR/Akt/mTOR signaling pathway by ANXA8. The present results provided evidence to support further investigation of the functional identification of ANXA8 in lung cancer cells in the future.

OX40 ligand levels and high-sensitivity C-reactive protein levels in blood from local coronary plaque and the femoral artery in patients with acute coronary syndrome or stable angina.

OX40 ligand (OX40L) and high-sensitivity C-reactive protein (hs-CRP) play important roles in the pathogenesis of atherosclerosis. In this study, consecutive patients with acute coronary syndrome (ACS; n = 90) or stable angina (SA; n = 40) and healthy control subjects (n = 50) were evaluated to assess plasma OX40L and serum hs-CRP levels in local coronary plaque and the femoral artery. OX40L and hs-CRP levels in the femoral artery were significantly higher in patients with ACS compared with controls. OX40L and hsCRP levels in local coronary plaque (OX40L(c) and hs-CRP(c), respectively) were significantly higher in ACS than in SA patients. OX40L and hs-CRP levels were positively correlated with each other and were also correlated with fibrinogen levels. The number of complex lesions was correlated with OX40L(c) and hs-CRP(c) levels. It is concluded that the OX40L(c) level was highly sensitive for evaluating the inflammatory response in ACS and elevated levels of OX40L(c) may be a valuable predictive marker for increased risk of atherosclerotic progression in ACS patients.

Niemann-Pick type C1 protein influences the delivery of cholesterol to the SREBP: SCAP complex

The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.