Maternally expressed gene 3 (MEG3) is an imprinted gene belonging to the imprinted DLK1–MEG3 locus located at chromosome 14q32.3 in humans. Its mouse ortholog, Meg3, also known as gene trap locus 2 (Gtl2), is located at distal chromosome 12. The MEG3 gene encodes a long noncoding RNA (lncRNA) and is expressed in many normal tissues. MEG3 gene expression is lost in an expanding list of primary human tumors and tumor cell lines. Multiple mechanisms contribute to the loss of MEG3 expression in tumors, including gene deletion, promoter hypermethylation, and hypermethylation of the intergenic differentially methylated region. Re-expression of MEG3 inhibits tumor cell proliferation in culture and colony formation in soft agar. This growth inhibition is partly the result of apoptosis induced by MEG3. MEG3 induces accumulation of p53 (TP53) protein, stimulates transcription from a p53-dependent promoter, and selectively regulates p53 target gene expression. Maternal deletion of the Meg3 gene in mice results in skeletal muscle defects and perinatal death. Inactivation of Meg3 leads to a significant increase in expression of angiogenesis-promoting genes and microvessel formation in the brain. These lines of evidence strongly suggest that MEG3 functions as a novel lncRNA tumor suppressor.

MEG3 is a maternally expressed imprinted gene suggested to function as a non-coding RNA. Our previous studies suggest that MEG3 has a function of tumor suppression. The tumor suppressor p53 plays a central role in tumor suppression and mediates the functions of many other tumor suppressors. Therefore, we hypothesized that MEG3 functions through activation of p53. We found that transfection of expression constructs for MEG3 and its isoforms results in a significant increase in p53 protein levels and dramatically stimulates p53-dependent transcription from a p53-responsive promoter. Using this as the functional assay, we demonstrated that the open reading frames encoded by MEG3 transcripts are not required for MEG3 function, and the folding of MEG3 RNA is critical to its function, supporting the concept that MEG3 functions as a non-coding RNA. We further found that MEG3 stimulates expression of the growth differentiation factor 15 (GDF15) by enhancing p53 binding to the GDF15 gene promoter. Interestingly, MEG3 does not stimulate p21 CIP1 expression, suggesting that MEG3 can regulate the specificity of p53 transcriptional activation. p53 degradation is mainly mediated by the mouse double minute 2 homolog (MDM2). We found that MDM2 levels were down-regulated in cells transfected with MEG3, suggesting that MDM2 suppression contributes at least in part to p53 accumulation induced by MEG3. Finally, we found that MEG3 is able to inhibit cell proliferation in the absence of p53. These data suggest that MEG3 non-coding RNA may function as a tumor suppressor, whose action is mediated by both p53-dependent and p53-independent pathways.

A central topic in single-atom catalysis is building strong interactions between single atoms and the support for stabilization. Herein we report the preparation of stabilized single-atom catalysts via a simultaneous self-reduction stabilization process at room temperature using ultrathin two-dimensional Ti3–x C2T y MXene nanosheets characterized by abundant Ti-deficit vacancy defects and a high reducing capability. The single atoms therein form strong metal–carbon bonds with the Ti3–x C2T y support and are therefore stabilized onto the sites previously occupied by Ti. Pt-based single-atom catalyst (SAC) Pt1/Ti3–x C2T y offers a green route to utilizing greenhouse gas CO2, via the formylation of amines, as a C1 source in organic synthesis. DFT calculations reveal that, compared to Pt nanoparticles, the single Pt atoms on Ti3–x C2T y support feature partial positive charges and atomic dispersion, which helps to significantly decrease the adsorption energy and activation energy of silane, CO2, and aniline, thereby boosting catalytic performance. We believe that these results would open up new opportunities for the fabrication of SACs and the applications of MXenes in organic synthesis.

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