Background
Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.
Methods
Bioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422.
Results
We characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells.
Conclusions
Circ_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.
It is a great challenge to directly grow super long all‐inorganic perovskite monocrystalline wires due to the weak surface energy difference among the low index facets. Here, a one‐pot solution process to grow the aspect ratio over 105 of monocrystalline CsPbBr3 perovskite wires (PWs) and yield up to 70% is reported. A chemical potential dependent surface energy difference amplification strategy is proposed to regulate the surface energy of growing and grown surfaces accordingly to the anisotropic growth of CsPbBr3. The anisotropic growth of wires is derived from the regulation of anti‐solvent diffusion kinetic and the mass transfer kinetic control of the metal halide salts. This experiment demonstrates a 50 times amplification of surface energy difference. As‐produced PWs present a high photodetection responsivity up to 4923 A W−1, external quantum efficiency exceeding 13 784%, and detectivity over 3.6 × 1013 Jones. This work not only reveals the mechanism of surface energy dominated anisotropic growth for CsPbBr3 PWs, but also elucidates the important role of kinetics regulation during the growth process, which may open a new window for the low‐dimensional crystal growth of ionic compounds.
BackgroundThe use of recombinant viral vectors expressing T. gondii antigens is a safe and efficient approach to induce immune responses against the parasite, as well as a valuable tool for vaccine development. We have previously prolonged the survival time of mice challenged with the RH strain of T. gondii by immunizing the mice with a eukaryotic vector expressing the protein ROP18 of T. gondii. We are now looking for ways to improve this vaccination strategy and enhance protection.MethodsIn this study, we constructed and characterized a novel recombinant canine adenovirus type 2 expressing ROP18 (CAV-2-ROP18) of T. gondii by cytopathic effect (CPE) and indirect immunofluorescence assay (IFA) following transfection into MDCK cells. Intramuscular immunization of Kunming mice with CAV-2-ROP18 was carried out to evaluate humoral and cellular immune responses.ResultsThe vaccination of experimental mice with CAV-2-ROP18 elicited antibody production against ROP18, including high levels of a mixed IgG1/IgG2a and significant production of IFN-γ or IL-2, and displayed a significant bias towards a helper T cell type 1 (Th1) profile. Furthermore, the presence of T. gondii-specific IFN-γ-production and TNF-α-production T cells was elicited in both CD4+ and CD8+ T cell compartments. Significantly higher survival rates (40%) occurred in the experimental group, and a reduction in brain cyst burden was detected in vaccinated mice.ConclusionThese results demonstrate the potential use of a CAV vector harboring the ROP18 gene in the development of a vaccine against acute and chronic toxoplasmosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0815-1) contains supplementary material, which is available to authorized users.
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