Background: Lung cancer (LC) is one of the most lethal and most prevalent malignant tumors, and its incidence and mortality are increasing annually. Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Several biomarkers have been confirmed by data excavation to be related to metastasis, prognosis and survival. However, the moderate predictive effect of a single gene biomarker is not sufficient. Thus, we aimed to identify new gene signatures to better predict the possibility of LUAD. Methods:Using an mRNA-mining approach, we performed mRNA expression profiling in large LUAD cohorts (n = 522) from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed, and connections between genes and glycolysis were found in the Cox proportional regression model. Results:We confirmed a set of nine genes (HMMR, B4GALT1, SLC16A3, ANGPTL4, EXT1, GPC1, RBCK1, SOD1, and AGRN) that were significantly associated with metastasis and overall survival (OS) in the test series. Based on this nine-gene signature, the patients in the test series could be divided into high-risk and low-risk groups. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the nine-gene signature is independent of clinical factors. Conclusion:Our study reveals a connection between the nine-gene signature and glycolysis. This research also provides novel insights into the mechanisms underlying glycolysis and offers a novel biomarker of a poor prognosis and metastasis for LUAD patients.

BackgroundLong non-coding RNAs (lncRNAs) have been identified as critical regulators in the development of atherosclerosis (AS). Here, we focused on discussing roles and molecular mechanisms of lncRNA H19 in vascular smooth muscle cells (VSMCs) progression.MethodsRT-qPCR assay was used to detect the expression patterns of H19 and miR-148b in clinical samples and cells. Cell proliferative ability was evaluated by CCK-8 and colony formation assays. Cell apoptotic capacity was assessed by apoptotic cell percentage and the caspase-3 activity. Bioinformatics analysis, luciferase and RNA immunoprecipitation (RIP) assays were employed to demonstrate cell percentage and the relationship among H19, miR-148b and wnt family member 1 (WNT1). Western blot assay was performed to determine expressions of proliferating cell nuclear antigen (PCNA), ki-67, Bax, Bcl-2, WNT1, β-catenin, C-myc and E-cadherin.ResultsThe level of H19 was increased and miR-148b expression was decreased in human AS patient serums and oxidized low-density lipoprotein (ox-LDL)-stimulated human aorta vascular smooth muscle cells (HA-VSMCs). H19 knockdown suppressed proliferation and promoted apoptosis in HA-VSMCs following the treatment of ox-LDL. H19 inhibited miR-148b expression by direct interaction. Moreover, miR-148b inhibitor could reverse the effects of H19 depletion on proliferation and apoptosis in ox-LDL-stimulated HA-VSMCs. Further mechanical explorations showed that WNT1 was a target of miR-148b and H19 acted as a competing endogenous RNA (ceRNA) of miR-148b to enhance WNT1 expression. Furthermore, miR-148 inhibitor exerted its pro-proliferation and anti-apoptosis effects through activating WNT/β-catenin signaling in ox-LDL-stimulated HA-VSMCs.ConclusionH19 facilitated proliferation and inhibited apoptosis through modulating WNT/β-catenin signaling pathway via miR-148b in ox-LDL-stimulated HA-VSMCs, implicating the potential values of H19 in AS therapy.

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Long non-coding RNA (lncRNA) dysregulation is involved in tumorigenesis and regulation of diverse cellular processes in gliomas. lncRNA SNHG12 is upregulated and promotes cell growth in human osteosarcoma cells. TAR-DNA binding protein 43 (TDP43) functions as an oncogene in various tumors by modulating RNA expression. Downregulation of TDP43 or SNHG12 significantly inhibited malignant biological behaviors of glioma cells. miR-195, downregulated in glioma tissues and cells, significantly impaired the malignant progression of glioma cells. TDP43 upregulated miR-195 in an SNHG12-dependent manner. We further revealed that SNHG12 and miR-195 were in an RNA-induced silencing complex (RISC). Inhibition of SNHG12 combined with restoration of miR-195 robustly reduced tumor growth in vivo. SOX5 was overexpressed in glioma tissues and cells. miR-195 targeted SOX5 3′ UTR in a sequence-specific manner. Gelsolin was activated by SOX5. More importantly, SOX5 activated SNHG12 promoter and upregulated its expression, forming a feedback loop. Dysregulation of SNHG12, miR-195, and SOX5 predicted poor prognosis of glioma patients. The present study demonstrated that SNHG12-miR-195-SOX5 feedback loop exerted a crucial role in the regulation of glioma cells’ malignant progression.

The Notch signaling pathway plays critical roles in human cancers, including osteosarcoma, suggesting that the discovery of specific agents targeting Notch would be extremely valuable for osteosarcoma. Curcumin, a naturally occurring phenolic compound found in curcuma longa, has been shown to inhibit proliferation and induce apoptosis of osteosarcoma cells in vitro and tumor growth in xenotransplant or orthotransplant models. However, the precise molecular mechanisms by which curcumin exerts its antitumor activity remain unclear. Here we used multiple molecular approaches, such as the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, the invasion assay, gene transfection, real‐time RT‐PCR, western blot and gelatin zymography, to investigate whether the downregulation of Notch‐1 contributes to curcumin‐induced inhibition of proliferation and invasion in osteosarcoma cells. The results showed that curcumin caused marked inhibition of osteosarcoma cell growth and G2/M phase cell cycle arrest. This was associated with concomitant attenuation of Notch‐1 and downregulation of its downstream genes, such as matrix metalloproteinases, resulting in the inhibition of osteosarcoma cell invasion through Matrigel. We also found that specific downregulation of Notch‐1 via small‐interfering RNA prior to curcumin treatment resulted in enhanced inhibition of cell growth and invasion. These results suggest that antitumor activity of curcumin is mediated through a novel mechanism involving inactivation of the Notch‐1 signaling pathway. Our data provide the first evidence that the downregulation of Notch‐1 by curcumin may be an effective approach for the treatment of osteosarcoma.

Planar cell polarity (PCP) signaling is essential in determining the polarity of cells within the plane of an epithelial sheet. Core PCP genes have been recently shown to control the global polarization of hair follicles in mice. Fuz, a homologue of the Drosophila PCP effector gene, fuzzy, is critical in ciliogenesis in vertebrates, and is required for the development of a wide range of organs in mice. Here, we report that disruption of the Fuz gene in mice severely blocked the development of hair follicles in the skin. In contrast to the loss of hair follicle polarization in mice deficient in core PCP genes, hair follicles in mice lacking the Fuz gene retained their typical anterior-posterior orientation. We show that disruption of Fuz impaired the formation of primary cilia and the hedgehog signaling pathway in the skin. In addition, using skin grafts and skin reconstitution assays we demonstrate that the expression of Fuz is required in both epidermal and dermal cells and that the formation of primary cilia is a cell-autonomous process that does not require cross talk between the epithelia and mesenchymal compartments during hair follicle formation.

1. The nystatin perforated-patch method was used to record macroscopic currents from antitrinitrophenyl (TNP) immunoglobulin E (IgE)-sensitized rat basophilic leukaemia (RBL-2H3) cells at 37 'C. 4. Two inorganic blockers of antigen-stimulated "5Ca2+ influx and secretion, La3+ and Zn2+, inhibited Ica by '50 % at concentrations known to produce 50 % block of "5Ca2+ influx. In contrast, cromolyn sodium (0 5 mM) and the L-type Ca2+ channel antagonist nitrendipine (5 /1M) had no effect on Ica.5. ICa also was induced by the intracellular Ca2+ mobilizer thapsigargin. Because the actions of thapsigargin and antigen were not additive, IgE receptor cross-linkage appears to activate the recently described capacitative Ca2+ entry channels.