Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.
Background
Cell therapy provides hope for treatment of advanced liver failure. Proliferating human hepatocytes (ProliHHs) were derived from primary human hepatocytes (PHH) and as potential alternative for cell therapy in liver diseases. Due to the continuous decline of mature hepatic genes and increase of progenitor like genes during ProliHHs expanding, it is challenge to monitor the critical changes of the whole process. Raman microspectroscopy is a noninvasive, label free analytical technique with high sensitivity capacity. In this study, we evaluated the potential and feasibility to identify ProliHHs from PHH with Raman spectroscopy.
Methods
Raman spectra were collected at least 600 single spectrum for PHH and ProliHHs at different stages (Passage 1 to Passage 4). Linear discriminant analysis and a two-layer machine learning model were used to analyze the Raman spectroscopy data. Significant differences in Raman bands were validated by the associated conventional kits.
Results
Linear discriminant analysis successfully classified ProliHHs at different stages and PHH. A two-layer machine learning model was established and the overall accuracy was at 84.6%. Significant differences in Raman bands have been found within different ProliHHs cell groups, especially changes at 1003 cm−1, 1206 cm−1 and 1440 cm−1. These changes were linked with reactive oxygen species, hydroxyproline and triglyceride levels in ProliHHs, and the hypothesis were consistent with the corresponding assay results.
Conclusions
In brief, Raman spectroscopy was successfully employed to identify different stages of ProliHHs during dedifferentiation process. The approach can simultaneously trace multiple changes of cellular components from somatic cells to progenitor cells.
Histone
posttranslational modifications (PTMs) are vital epigenetic
regulators in many fundamental cell signaling pathways and diverse
biological processes. Histone lysine benzoylation is a recently identified
epigenetic mark associated with active transcription; however, it
remains to be explored. Herein, we first report the genetic encoding
of benzoyllysine and fluorinated benzoyllysines into full-length histone
proteins in a site-specific manner in live cells, based on our rationally
designed synthetase and fine-integrated fluorine element into benzoyllysines.
The incorporated unnatural amino acids integrating unique features
were demonstrated as versatile probes for investigating histone benzoylation
under biological environments, conferring multiplex signals such
as 19F NMR spectra with chemical clarity and fluorescence
signals for benzoylation. Moreover, the site specifically incorporated
lysine benzoylation within native full-length histone proteins revealed
distinct dynamics of debenzoylation in the presence of debenzoylase
sirtuin 2 (SIRT2). Our developed strategy for genetic encoding of
benzoyllysines offers a general and novel approach to gain insights
into interactions of site-specific histone benzoylation modifications
with interactomes and molecular mechanisms in physiological settings,
which could not be accessible with fragment histone peptides. This
versatile chemical tool enables a direct and new avenue to explore
benzoylation, interactions, and histone epigenetics, which will provide
broad utilities in chemical biology, protein science, and basic biology
research.
Urinary bladder cancer (UBC) is a common malignant tumor with high incidence. Advances in the diagnosis and treatment of this disease demand the identification of novel therapeutic targets. Multiple studies demonstrated that PDE4B level was upregulated in malignancies and high PDE4B expression was correlated with poor outcomes. Herein, we identified that PDE4B was a potential therapeutic target in UBC. We confirmed that PDE4B expression was correlated with aggressive clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ectopic expression of PDE4B promoted UBC cells proliferation, migration and invasion, whereas PDE4B depletion suppressed cancer cell aggressiveness. We also identified CBX7 as a regulator of PDE4B to suppress the expression of PDE4B at the transcription level in a PRC1-dependent manner. Moreover, our results indicated that PDE4B induced epithelial-to-mesenchymal transition (EMT) in UBC cells via β-catenin pathway, whereas inhibition of PDE4B by its small molecule inhibitor, rolipram, effectively reversed the PDE4B overexpression-induced effects. To sum up, our results indicated that PDE4B acts as an oncogene by promoting UBC cell migration and invasion via β-catenin/EMT pathway.
In permafrost regions, long distance buried pipelines are widely used to transport oil and natural gas resources. However, pipeline problems occur frequently due to the complicated surrounding environment and transportation requirement of positive temperature. In this study, a thermal insulation layer was applied to mitigate permafrost degeneration around the buried oil-gas pipelines. Based on engineering background of the Sebei-Xining-Lanzhou natural gas pipeline in China, an indoor model test was designed and carried out in which many key indices, such as the temperature regime, vertical displacement, pipeline wall stress, and water content, were closely monitored. The test results indicate that the large heat loss of the buried pipeline produces a rapid increase in ground temperatures which seriously reduces the bearing capacity of the permafrost foundation. The buried oil-gas pipelines with a thermal insulation layer can effectively reduce the thawing range and vertical displacement of the permafrost foundation around the buried pipelines, so as to control the stress of the pipeline wall in the normal range and protect the safe and stable operation of the buried oil-gas pipelines. The experimental results can serve as a reference for the construction, operation, and maintenance of buried oil-gas pipelines in permafrost regions.
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