piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD

Incorporation of Microbial Functional Traits in Biogeochemistry Models Provides Better Estimations of Benthic Denitrification and Anammox Rates in Coastal Oceans

Marine benthic nitrogen (N) cycling may vary widely across space and seasons; it is thus needed to make high-resolution estimations of these important ecosystem processes with a reasonable number of variables. In this study, we determined the benthic denitrification and anammox potentials in two basins, the Bohai Sea and the North Yellow Sea of China in May and November, and evaluated models in predicting these functions with environmental factors and/or microbial gene-based functional traits. We found that denitrification generally dominated the N loss (54-98%), and that the denitrification rate varied greatly between basins and seasons. The anammox rate was generally higher in the Bohai Sea than in the North Yellow Sea in both seasons, and it made a greater contribution in November (22%) than in May (16%). Among the measured environmental factors, chlorophyll a in bottom waters and sedimentary organic carbon content were the most influential for predicting denitrification and anammox rates, respectively. On the other hand, the alpha diversities and gene abundances of involved bacteria were poorly correlated with the function potentials, indicating that these functional traits could not well explain the functions alone. Upon the incorporation of two gene copy number ratios [nosZ/(nirS+nirK) and nirK/bacterial 16S rRNA genes] into the environmental factor-parameterized models, however, we found that the predictive powers of the regression models for total N loss, denitrification and anammox rates, and contributions of anammox increased substantially, indicating that taking microbial functional traits into account could make estimations of these N-cycling functions in coastal ecosystems more accurate

TGF-β1-induced miR-503 controls cell growth and apoptosis by targeting PDCD4 in glioblastoma cells

Abstract Aberrant expression of microRNAs hae been shown to be closely associated with glioblastoma cell proliferation, apoptosis and drug resistance. However, mechanisms underlying the role of mcroRNAs in glioblastoma cell growth and apoptosis are not fully understood. In this study, we report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-β1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. Ectopic overexpression of miR-503 promotes cell growth and inhibits apoptosis by targeting PDCD4. In contrast, inhibition of miR-503 reduces cell growth. Furthermore, miR-503 inhibitor augments the growth inhibitory effect of temozolomide in glioblastoma cells. These results establish miR-503 as a promising molecular target for glioblastoma therapy

Contrasting spatiotemporal patterns and environmental drivers of diversity and community structure of ammonia oxidizers, denitrifiers, and anammox bacteria in sediments of estuarine tidal flats

The spatial and temporal patterns of diversity, community structure, and their drivers are fundamental issues in microbial ecology. This study aimed to investigate the relative importance of spatial and seasonal controls on the distribution of nitrogen cycling microbes in sediments of estuarine tidal flats, and to test the hypothesis that metals impact the distribution of nitrogen-cycling microbes in the coastal system. Two layers of sediment samples were collected from three estuarine tidal flats of Laizhou Bay in 2010 winter and 2011 summer. The alpha diversities (Shannon and Simpson indices) and community structure of ammonia oxidizing bacteria (AOB) and archaea (AOA), denitrifier and anammox bacteria (AMB) were revealed using denaturing gradient gel electrophoresis and clone library analysis of amoA, nosZ and 16S rRNA gene markers. We found that both AOB and AMB exhibited distinct seasonal patterns in either alpha diversity or community turnover; AOA had different alpha diversities in two layers, but neither spatial nor seasonal patterns were found for their community turnover. However, no distinct spatiotemporal pattern was observed for either diversity or community composition of nosZ-type denitrifiers. For correlations between alpha diversities and environmental factors, significant correlations were found between AOB and ammonium, temperature and As, between denitrifiers and nitrite, salinity and Pb, and between AMB and Pb, ratio of organic carbon to nitrogen, ammonium, pH and dissolved oxygen. Salinity and sediment grain size were the most important factors shaping AOB and AOA communities, respectively; whereas AMB community structure was mostly determined by temperature, dissolved oxygen, pH and heavy metals As and Cd. These results stress that ammonia oxidizers, denitrifiers and anammox bacteria have generally different distributional patterns across time and space, and heavy metals might have contributed to their differentiated distributions in coastal sediments.The spatial and temporal patterns of diversity, community structure, and their drivers are fundamental issues in microbial ecology. This study aimed to investigate the relative importance of spatial and seasonal controls on the distribution of nitrogen cycling microbes in sediments of estuarine tidal flats, and to test the hypothesis that metals impact the distribution of nitrogen-cycling microbes in the coastal system. Two layers of sediment samples were collected from three estuarine tidal flats of Laizhou Bay in 2010 winter and 2011 summer. The alpha diversities (Shannon and Simpson indices) and community structure of ammonia oxidizing bacteria (AOB) and archaea (AOA), denitrifier and anammox bacteria (AMB) were revealed using denaturing gradient gel electrophoresis and clone library analysis of amoA, nosZ and 16S rRNA gene markers. We found that both AOB and AMB exhibited distinct seasonal patterns in either alpha diversity or community turnover; AOA had different alpha diversities in two layers, but neither spatial nor seasonal patterns were found for their community turnover. However, no distinct spatiotemporal pattern was observed for either diversity or community composition of nosZ-type denitrifiers. For correlations between alpha diversities and environmental factors, significant correlations were found between AOB and ammonium, temperature and As, between denitrifiers and nitrite, salinity and Pb, and between AMB and Pb, ratio of organic carbon to nitrogen, ammonium, pH and dissolved oxygen. Salinity and sediment grain size were the most important factors shaping AOB and AOA communities, respectively; whereas AMB community structure was mostly determined by temperature, dissolved oxygen, pH and heavy metals As and Cd. These results stress that ammonia oxidizers, denitrifiers and anammox bacteria have generally different distributional patterns across time and space, and heavy metals might have contributed to their differentiated distributions in coastal sediments