A Novel ATM Antisense Transcript ATM-AS Positively Regulates ATM Expression in Normal and Breast Cancer Cells

Objective:The ataxia telangiectasia mutated(ATM)gene is a master regulator in cellular DNA damage response.The dysregulation of ATM expression is frequent in breast cancer,and is known to be involved in the carcinogenesis and prognosis of cancer.However,the underlying mechanism remains unclear.The bioinformatic analysis predicted a potential antisense transcript ATM-antisense(AS)from the opposite strand of the ATM gene.The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATM gene regulation.Methods:Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATM gene locus.qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples.Luciferase reporter gene assays,biological mass spectrometry,ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression.Immunofluorescence and host-cell reactivation(HCR)assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair.Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients.Results:The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter.The reduced ATM-AS level led to the abnormal downregulation of ATM expression,and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro.The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples,and the patient prognosis.Conclusion:The present study demonstrated that ATM-AS,an antisense transcript located within the ATM gene body,is an essential positive regulator of ATM expression,and functions by mediating the binding of KAT5 to the ATM promoter.These findings uncover the novel mechanism underlying the dysregulation of the ATM gene in breast cancer,and enrich our understanding of how an antisense transcript regulates its host gene.

Facile one-step synthesis of PdPb nanochains for high-performance electrocatalytic ethanol oxidation

The widespread application of direct ethanol fuel cells is hampered due to the low activity,high cost and poor operation durability of electrocatalysts for ethanol oxidation reaction(EOR).Herein,we report a one-pot synthetic method to synthesize PdPb3 nanochains with well-defined shape,size and composition via a solution-phase reduction method.The morphology,composition distribution and structure characteristics of PdPb3 nanochains were investigated by transmission electron microscopy,X-ray photoelectron spectroscopy and X-ray diffraction.Thanks to the unique structure,the as-obtained PdPb3 nanochains can manifest much higher mass activity(2523 mA·mg-1)and higher operation durability than commercial Pd/C(1272 mA·mg-1)during the EOR measurements.More importantly,further CO-stripping measurements indicate that the incorporation of Pb species could favor the oxidative removal of CO intermediates on the Pd electrode at the negative potential and enhance the EOR activity and stability,making it possible to develop highly active and durable electrocatalysts.

Synthesis and characterization of carbazole-based dendrimers as bipolar host materials for green phosphorescent organic light emitting diodes

A group of novel, carbazole-based dendrimers comprised of the electron-accepting dibenzothiophene core and the electron-donating oligo-carbazole dendrons, namely G1 SF and G2 SF, are synthesized utilizing the Ullmann C–N coupling reaction. The dendrimers are designed in such a way to show good solubility in common organic solvents, excellent thermochemical stability with decomposition temperatures（Td） up to430 8C, and high HOMO levels in a range from 5.45 e V to 5.37 e V. Results of density functional theory calculations（DFT） indicate G2 SF has an almost complete separation of HOMO and LUMO levels at the holeand electron-transporting moieties; while G1 SF exhibits only partial separation of the HOMO and LUMO levels possibly due to intramolecular charge transfer. Green phosphorescent OLEDs were fabricated by the spin coating method with the dendrimers as hosts and traditional green iridium phosphor as doped emitter. Under ambient conditions, a maximum luminance efficiency（hL） of 19.83 cd A^-1and a maximum external quantum efficiency of 5.85% are achieved for G1 SF, and 15.50 cd A ^-1and 4.57% for G2 SF.