METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

B, N Co-Doping Sequence: An Efficient Electronic Modulation of the Pd/MXene Interface with Enhanced Electrocatalytic Properties for Ethanol Electrooxidation.

Improving the electrocatalytic properties by regulating the surface electronic structure of supported metals has always been a hot issue in electrocatalysis. Herein, two novel catalysts Pd/B-N-Ti3C2 and Pd/N-B-Ti3C2 are used as the models to explore the effect of the B and N co-doping sequence on the surface electronic structure of metals, together with the electrocatalytic properties of ethanol oxidation reaction. The two catalysts exhibit obviously stratified morphology, and the Pd nanoparticles having the same amount are both uniformly distributed on the surface. However, the electron binding energy of Ti and Pd elements of Pd/B-N-Ti3C2 is smaller than that of Pd/N-B-Ti3C2. By exploring the electrocatalytic properties for EOR, it can be seen that all the electrochemical surface area, maximum peak current density, and antitoxicity of the Pd/B-N-Ti3C2 catalyst are much better than its counterpart. Such different properties of the catalysts can be attributed to the various doping species of B and N introduced by the doping sequence, which significantly affect the surface electronic structure and size distribution of supported metal Pd. Density functional theory calculations demonstrate that different B-doped species can offer sites for the H atom from CH3CH2OH of dehydrogenation in Pd/B-N-Ti3C2, thereby facilitating the progress of the EOR to a favorable pathway. This work provides a new insight into synthesizing the high-performance anode materials for ethanol fuel cells by regulating the supported metal catalyst with multielement doping.