Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Background

Long noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown.

Methods

HOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve.

Results

Among the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663–0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906–0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = ?0.124, P = 0.048) and lung adenocarcinoma (r = ?0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA.

Conclusions

Our results showed that the gene profiles were significantly changed after HOXA11-AS knock-down in NSCLC cells. We speculated that HOXA11-AS may play an important role in NSCLC development and progression by regulating the expression of various pathways and genes, especially DOCK8 and TGF-beta pathway. However, the exact mechanism should be verified by functional experiments.

     

Strigolactones regulate protonema branching and act as a quorum sensing-like signal in the moss Physcomitrella patens

Strigolactones are a novel class of plant hormones controlling shoot branching in seed plants. They also signal host root proximity during symbiotic and parasitic interactions. To gain a better understanding of the origin of strigolactone functions, we characterised a moss mutant strongly affected in strigolactone biosynthesis following deletion of the CAROTENOID CLEAVAGE DIOXYGENASE 8 (CCD8) gene. Here, we show that wild-type Physcomitrella patens produces and releases strigolactones into the medium where they control branching of protonemal filaments and colony extension. We further show that Ppccd8 mutant colonies fail to sense the proximity of neighbouring colonies, which in wild-type plants causes the arrest of colony extension. The mutant phenotype is rescued when grown in the proximity of wild-type colonies, by exogenous supply of synthetic strigolactones or by ectopic expression of seed plant CCD8. Thus, our data demonstrate for the first time that Bryophytes (P. patens) produce strigolactones that act as signalling factors controlling developmental and potentially ecophysiological processes. We propose that in P. patens, strigolactones are reminiscent of quorum-sensing molecules used by bacteria to communicate with one another.     

Nitrous oxide emissions from surface flow and subsurface flow constructed wetland microcosms: Effect of feeding strategies

The effects of continuous and intermittent feeding strategies on nitrogen removal and N₂O emission from surface flow and subsurface flow constructed wetlands were evaluated in this study. Microcosm wetlands planted with Phragmites australis were constructed and operated with different feeding strategies for the 4-month experiment. Results showed the intermittent feeding strategy could enhance the removal of ammonium effectively in the subsurface flow constructed wetlands, although it had no significant effect for the surface flow wetlands. And the intermittent feeding mode could promote the emission of N₂O. The amount of N₂O-N emission from the subsurface flow constructed wetlands with intermittent feeding mode was about 5 times higher than that with continuous feeding strategy and the emission rate ranged from 0.09 ± 0.03 to 7.33 ± 1.49 mg/m²/h. Compared with the surface flow constructed wetlands, the N₂O emission in the subsurface flow constructed wetlands was affected significantly by the intermittent feeding mode.     

Assembly of dandelion-like Au/PANI nanocomposites and their application as SERS nanosensors

The monodisperse, uniform dandelion-like Au/polyaniline (PANI) composite nanospheres were synthesized by a simple one-step process without any additives or templates. The nanospheres are really composed of many short nanorods and the average diameter of whole nanospheres is about 180 nm. The morphology of Au/PANI composites could be controlled by adjusting the molar ratio of HAuCl(4) to aniline. The prepared nanocomposite is developed as a wonderful sensor for the detection of Hg(2+) ions, which is based upon the Raman intensity response of PANI to Hg(2+) ions. Results from the morphology-dependent sensitivity investigations show that the dandelion-like nanospheres have an ultra sensitive response (as low as 10(-11)M) compared with other morphologies. The nanosensor also exhibits good reproducibility and greater selectivity for Hg(2+) ions than the other heavy metal ions. And the mechanism was proposed. The proposed nanosensors can be applied for highly sensitive and selective chemical analysis in a variety of environmental detection.     

Effects of enamel matrix proteins on proliferation, differentiation and attachment of human alveolar osteoblasts

Objectives: Enamel matrix proteins (EMPs) have been demonstrated to promote periodontal regeneration. However, effects of EMPs on human alveolar osteoblasts (hAOBs), up to now, have still been unclear. The purpose of this study was to investigate influence of EMPs on proliferation, differentiation and attachment of hAOBs in vitro. Materials and methods: EMPs were extracted using the acetic acid method, hAOBs were obtained and cultured in vitro. Cell proliferation, alkaline phosphatase (ALP) activity, mRNA expression of osteogenic markers and cell attachment were measured in the absence and in the presence of EMPs (50, 100 and 200 μg/ml). Results: EMPs increased proliferation of hAOBs; however, they inhibited ALP activity and mRNA expression of osteogenic markers (collagen I, ALP, runt‐related protein 2, osteocalcin, bone sialoprotein and osteopontin). Meanwhile, EMPs hindered hAOBs’ attachment. These effects occurred in EMPs concentration‐dependent manner. Conclusions: These results indicate that EMPs may inhibit osteoblastic differentiation and attachment to prevent ankylosis and allow other cell types to regenerate periodontal tissues.     

Oxalate production at different initial Pb²+ concentrations and the influence of oxalate during solid-state fermentation of straw with Phanerochaete chrysosporium

The production of oxalate at different initial Pb²⁺ concentrations during solid-state fermentation of straw with Phanerochaete chrysosporium was investigated. It was found that the maximal peak value of oxalate concentration (22.84 mM) was detected at the initial Pb²⁺ concentration of 200 mg kg⁻¹ dry straw, while the minimum (15.89 mM) at the concentration of 600 mg Pb²⁺ kg⁻¹ dry straw, and at moderate concentration of Pb²⁺ the capability of oxalic acid secretion was enhanced. In addition, it was also found that more oxalic acid accumulation went together with better Pb²⁺ passivation effect and higher manganese peroxidase (MnP) activity. The present findings will improve the understandings of the interactions of heavy metals with white-rot fungi and the role of oxalate in lignin degradation system, which could provide useful references for more efficient treatment of Pb-contaminated lignocellulosic waste.     

Hedgehog signaling in skin cancers

An increasing progress on the role of Hedgehog (Hh) signaling for carcinogenesis has been achieved since the link of Hh pathway to human cancer was firstly established. In particular, the critical role of Hh signaling in the development of Basal cell carcinoma (BCC) has been convincingly demonstrated by genetic mutation analyses, mouse models of BCCs, and successful clinical trials of BCCs using Hh signaling inhibitors. In addition, the Hh pathway activity is also reported to be involved in the pathogenesis of Squamous Cell Carcinoma (SCC), melanoma and Merkel Cell Carcinoma. These findings have significant new paradigm on Hh signaling transduction, its mechanisms in skin cancer and even therapeutic approaches for BCC. In this review, we will summarize the major advances in the understanding of Hh signaling transduction, the roles of Hh signaling in skin cancer development, and the current implications of “mechanism-based” therapeutic strategies.     

Neurexins and Neuroligins: Recent Insights from Invertebrates

During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results relate to studies in mammals.