Search

MicroRNAs (miRs) play critical roles in cancer development, proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration through regulating the expression of oncogenes and tumour suppressor genes. Previous studies have indicated that miR-200c acts as a tumour suppressor in various cancers by downregulating high-mobility group box 1 (HMGB1) and thereby suppressing EMT and metastasis. In addition, miR-200c was reported to be downregulated and correlated with poor outcomes in non-small cell lung cancer (NSCLC). However, its functional role in HMGB1 regulation in NSCLC is still unclear. This study aimed to clarify whether miR-200c acts as a tumour suppressor in NSCLC by downregulating HMGB1, which is associated with EMT, invasion, cytoskeleton rearrangement, and migration in vitro and in vivo. In order to demonstrate HMGB1 downregulation by miR-200c, the NSCLC cell line A549 was transfected with miR-200c mimic or inhibitor. The mimic significantly reduced HMGB1 expression and suppressed EMT, invasion, and migration, while the inhibitor generated the opposite effects. Additionally, using xenograft mouse models, we confirmed that HMGB1 overexpression increased tumour EMT. In summary, our results demonstrated that miR-200c could suppress EMT, invasion, and migration of NSCLC cells by downregulating HMGB1.

This study aimed to evaluate changes in tibial bone speed of sound (SOS) over time, in preterm and term infants during infancy, in addition to identifying factors influencing the development of tibial SOS during infancy. Preterm (n = 155) and term (n = 65) infants were enrolled in this study. Tibial bone SOS was measured using quantitative ultrasonography (QUS) on the left tibia of newborn infants after birth (within 7 days), at 1 month old, and then every 2 months until subjects were approximately 12-15 months old. Follow-up checks included anthropometric measurements and tibial bone SOS. Mean tibial bone SOS at birth was significantly higher in term infants (mean ± SD, 2968.5 ± 99.7 m/s) than in preterm infants (2912.2 ± 122.6 m/s). Values of follow-up tibial bone SOS declined for the first 4 months, and then increased gradually until 12-15 months old. This increasing trend was greater in preterm infants after 2 months of corrected age than in term infants. There were no significant differences by 12-15 months of age between preterm and term infants. A longitudinal mixed-effect model controlling for internal correlations and other covariates in the two groups showed that age and the SOS value at birth were important factors affecting the tibial bone SOS in both preterm and term newborn infants during infancy. There are significant differences in the pattern of change in tibial bone SOS values between preterm and term infants during the first 12-15 months of life. Age and SOS value at birth were important factors affecting the pattern of tibial bone SOS change in both preterm and term newborn infants during infancy.

Pigment epithelium-derived factor (PEDF) is a multifunctional protein that exhibits anti-angiogenic, antitumor, anti-inflammatory, antioxidative, anti-atherogenic, and cardioprotective properties. While it was recently shown that PEDF expression is inhibited under low oxygen conditions, the functional role of PEDF in response to hypoxia/reoxygenation (H/R) remains unclear. The goal of this study was to therefore investigate the influence of PEDF on myocardial H/R injury. For these analyses, PEDF-specific small interfering RNA-expressing and PEDF-expressing lentivirus (PEDF-LV) vectors were utilized to knockdown or stably overexpress PEDF, respectively, within human cardiomyocytes (HCM) in vitro. We noted that reactive oxygen species (ROS) play important roles in the induction of cell death pathways, including apoptosis and autophagy in ischemic hearts. Our findings demonstrate that overexpression of PEDF resulted in a significant reduction in ROS production and attenuation of mitochondrial membrane potential depletion under H/R conditions. Furthermore, PEDF inhibited the activation of a two-step apoptotic pathway in which caspase-dependent (caspase-9 and caspase-3) and caspase-independent (apoptosis inducing factor and endonuclease G), which in turn cleaves several crucial substrates including the DNA repair enzyme poly (ADP-ribose) polymerase. Meanwhile, overexpression of PEDF also promoted autophagy, a process that is typically activated in response to H/R. Therefore, these findings suggest that PEDF plays a critical role in preventing H/R injury by modulating anti-oxidant and anti-apoptotic factors and promoting autophagy.

Adipose tissue is now considered as an endocrine organ involved in metabolic and inflammatory reactions. Adiponectin, a 244-amino acid peptide hormone, is associated with insulin resistance and carcinogenesis. Curcumin (diferuloylmethane) is the principal curcuminoid of the popular Indian spice, turmeric. Curcumin possesses antitumor effects, including the inhibition of neovascularization and regulation of cell cycle and apoptosis. However, the effects of adiponectin and curcumin on non-small cell lung cancer (NSCLC) remain unclear. In this study, we evaluated the expression of adiponectin in paired tumors and normal lung tissues from 77 patients with NSCLC using real-time polymerase chain reaction, western blotting, and immunohistochemistry. Kaplan-Meier survival analysis showed that patients with low adiponectin expression ratio (1) (p = 0.015). Curcumin inhibited the migratory and invasive ability of A549 cells via the inhibition of adiponectin expression by blocking the adiponectin receptor 1. Curcumin treatment also inhibited the in vivo tumor growth of A549 cells and adiponectin expression. These results suggest that adiponectin can be a prognostic indicator of NSCLC. The effect of curcumin in decreasing the migratory and invasive ability of A549 cells by inhibiting adiponectin expression is probably mediated through NF-κB/MMP pathways. Curcumin could be an important potential adjuvant therapeutic agent for lung cancer in the future.

Heat-shock proteins (HSPs) are molecular chaperones that protect proteins from damage. HSP27 expression is associated with cancer transformation and invasion. Ginkgo biloba extract (EGb761), the most widely sold herbal supplement, has antiangiogenic effects and induces tumor apoptosis. Data regarding the effect of EGb761 on HSP expression is limited, particularly in cancer. HSP27 expression in paired tumors and normal lung tissues of 64 patients with non-small cell lung cancer (NSCLC) were detected by real-time PCR, western blotting, and immunohistochemistry. NSCLC cell lines (A549/H441) were used to examine the migratory abilities in vitro. NSCLC tissue showed higher HSP27 expression than normal lung tissue. Kaplan-Meier survival analysis showed that NSCLC patients with low HSP27 expression ratio (1) (p = 0.04). EGb761 inhibited HSP27 expression and migratory ability of A549/H441 cells, which is the same as HSP27-siRNA transfection effect. Moreover, EGb761 treatment activated the AKT and p38 pathways and did not affect the expression of PI3K, ERK, and JNK pathways. HSP27 is a poor prognostic indicator of NSCLC. EGb761 can decrease the migration ability of A549/H441 by inhibiting HSP27 expression most likely through AKT and p38 MAPK pathways activation.