Overexpression of Activating Transcription Factor-2 (ATF-2) Activates Wnt/Ca2+ Signaling Pathways and Promotes Proliferation and Invasion in Non-Small-Cell Lung Cancer.

Previous studies have suggested an association of the expression of activating transcription factor-2 (ATF-2) with the survival time and the activity of the Wnt/Ca2+ signaling pathway in non-small-cell lung cancer (NSCLC). However, the exact role of ATF-2 in tumorigenesis and its underlying mechanism remains unclear. In this study, we study whether ATF-2 regulates the growth and reproduction of NSCLC cells through the Wnt/Ca2+ pathway. The expression of ATF-2 and pathway-related genes in non-small-cell lung cancer was detected by qRT-PCR and Western blotting. CRISPR/Cas9 technology was used to knock out the ATF-2 gene, and pathway inhibitors and agonists were added to induce cultured cells. The expression of pathway genes and the proliferation and invasion ability of A549 lung cancer cells were analyzed. ATF-2 and pathway-related genes were upregulated in NSCLC. The proliferation and invasion ability of A549 lung cancer cells was decreased after only adding pathway inhibitors. The expression of Wnt/Ca2+ pathway protein was decreased when the ATF-2 gene was knocked out, but the expression of Wnt/Ca2+ pathway protein was reversed after the addition of a pathway agonist. These results suggest that ATF-2 acts as an agonist in the Wnt/Ca2+ signaling pathway, promoting the expression of Wnt5a, Wnt11, CaMK II, and NLK in the Wnt/Ca2+ pathway, thereby regulating the proliferation and invasion of NSCLC cells.

Long non-coding RNA LINC00488 facilitates thyroid cancer cell progression through miR-376a-3p/PON2.

OBJECTIVE: Long non-coding RNAs (lncRNAs) recently have been identified as influential indicators in a variety of malignancies. The aim of the present study was to identify a functional lncRNA LINC00488 and its effects on thyroid cancer in the view of cell proliferation and apoptosis. METHODS: In order to evaluate the effects of LINC00488 on the cellular process of thyroid cancer, we performed a series of in vitro experiments, including cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, transwell chamber assay, Western blot and RT-qPCR. The target gene of LINC00488 was then identified by bioinformatics analysis (DIANA and TargetScan). Finally, a series of rescue experiments was conducted to validate the effect of LINC00488 and its target genes on proliferation, migration, invasion and apoptosis of thyroid cancer. RESULTS: Our findings revealed that LINC00488 was highly expressed in thyroid cancer cell lines (BCPAP, BHP5-16, TPC-1 and CGTH-W3) and promoted the proliferation, migration and invasion, while inhibited the apoptosis of thyroid cancer cells (BCPAP and TPC-1). The results of bioinformatics analysis and dual luciferase reporter gene assay showed that LINC00488 could directly bind to miR-376a-3p and down-regulated the expression level of miR-376a-3p. In addition, Paraoxonase-2 (PON2) was a target gene of miR-376a-3p and negatively regulated by miR-376a-3p. Rescue experiment indicated that LINC00488 might enhance PON2 expression by sponging miR-376a-3p in thyroid cancer. CONCLUSION: Taken together, our study revealed that lncRNA LINC00488 acted as an oncogenic gene in the progression of thyroid cancer via regulating miR-376a-3p/PON2 axis, which indicated that LINC00488-miR-376a-3p-PON2 axis could serve as novel biomarkers or potential targets for the treatment of thyroid cancer.

Molecular insights into the thermal stability of gold superlattices.

Atomistic molecular dynamics simulations are performed to study the thermal stability of bulk superlattices consisting of alkylthiol-coated gold nanocrystals. Using nanocrystals passivated by dodecanethiol chains, we show that the gold superlattice possesses a remarkable high-temperature stability, in agreement with experiment. When heated from room temperature, the superlattice expands slightly at lower temperature (<500 K) and then exhibits a considerable lattice contraction above 500 K, while maintaining the intact crystal structure up to 710 K. Once the temperature increases above 720 K, the gold superlattice becomes structurally unstable due to the local sintering of adjacent nanocrystals. Continuous heating to 750 K drives a large number of gold nanocrystals to coalesce and finally results in a tremendous destruction of the superstructure. The structural change and instability of superlattice are mainly attributed to the ligand desorption from nanocrystal surface induced by the variation in temperature. Furthermore, longer ligand length can effectively improve the thermal stability of gold superlattices. These findings are expected to provide a deep microscopic understanding of the thermal stability of superlattice materials.

Thrombocytopenia and GBA gene mutation in a patient with adult type 1 Gaucher disease.

A 38-year-old female patient was diagnosed with anemia for 3 years. Medical examination showed slight splenomegaly (250 × 62 mm), thrombocytopenia (platelets 51 × 109/L), anemia (Hb levels 107 g/L), and ß-glucocerebrosidase activity (GBA) in leukocytes was lower than normal. Microscopic findings of bone marrow smear demonstrated that Gaucher cells in bone marrow and periodic acid-Schiff staining of them were positive. Sequencing of GBA genomic and cDNA identified one novel homozygous mutation, c.484A> G (p.Met162Val). This case suggests that we should pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia and one novel homozygous mutation in GBA gene was reported for the first time. The novel mutation in homozygosity is apparently associated with mild, non-neuronopathic type 1 disease which is relatively uncommon in Asian populations.

VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis.

BACKGROUND: Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). MATERIAL/METHODS: Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. RESULTS: The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). CONCLUSIONS: Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA.

[Effect of curcumin combined with ATRA on differentiation of ATRA-resistant acute promyelocytic leukemia cells].

In order to investigate the effect of curcumin combined with all-trans retinoid acid (ATRA) on differentiation of ATRA-resistant acute promyelocytic leukemia (APL) cells and its molecular mechanism, the NB4-R1, an ATRA-resistant APL cells, was used as a model, counting of NB4-R1 and cell morphologic observation were performed, the effect of curcumin alone or combined with ATRA on proliferation, differentiation of NB4-R1 cells was detected by flow cytometry (FCM), the change of AKT phosphorylation in cell differentiation was detected by Western blot. The results showed that ATRA had no influence on NB4-R1 cell proliferation, but enhanced the inhibitory effect of curcumin on NB4-R1 cell growth; the curcumin or ATRA alone did not affect NB4-R1 differentiation; curcumin combined with ATRA could obviously induce CD11b expression; the cell morphology showed obvious differentiation characteristics. ATRA could promote phosphorylation of AKT in NB4 cells at short time, but not had effect on phosphorylation of AKT in NB4-R1 cells; the curcumin could enhance the phosphorylation of AKT in NB4-1R cells, the curcumin combined with ATRA could further enhance the phosphorylation of AKT. It is concluded that PI3K/AKT pathway inactivation may be one of the factors of drug resistance in APL and curcumin promotes differentiation of NB4-R1 through activating PI3K/AKT pathway.